3,360
Views
62
CrossRef citations to date
0
Altmetric
Review Article

Drug metabolism and pharmacokinetics

, , , , , , & show all
Pages 344-390 | Received 27 Feb 2009, Accepted 12 Mar 2009, Published online: 15 Jul 2009

References

  • Abdel-Razzak, Z., Loyer, P., Fautrel, A., Gautier, J.C., Corcos, L., Turlin, B., et al. (1993). Cytokines downregulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture. Mol Pharmacol 44:707–715.
  • Ahmed, I., Gokhale, R.D., Shah, M.V., Patton, T.F. (1987). Physicochemical determinants of drug diffusion across the conjunctiva, sclera and cornea. J Pharm Sci 76:583–586.
  • Aps, C., Reynolds, F. (1978). An intradermal study of the local anaesthetic and vascular effects of the isomers of bupivacaine. Br J Clin Pharmacol 6:63–68.
  • Arand, M., Cronin, A., Oesch, F., Mowbray, S.L., Jones, T.A. (2003). The telltale structures of epoxide hydrolases. Drug Metab Rev 35:365–383.
  • Arora, P., Sharma, S., Garg, S. (2002). Permeability issues in nasal drug delivery. Drug Deliv Today 7:967–975.
  • Awni, W.M., Locke, C., Dube, L.M., Cavanaugh, J.H. (1997). Evaluation of the diurnal variation in the pharmacokinetics of zileuton in healthy volunteers. J Clin Pharmacol 37:388–394.
  • Ayrton, A., Morgan, P. (2008). Role of transport proteins in drug discovery and development: a pharmaceutical perspective. Xenobiotica 38:676–708.
  • Babu, E., Takeda, M., Narikawa, S., Kobayashi, Y., Enomoto, A., Tojo, A., et al. (2002). Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta 1590(1–3):64–75.
  • Balani, S.K., Xu, X., Pratha, V., Koss, M.A., Amin, R.D., Dufresne, C., et al. (1997). Metabolic profiles of montelukast sodium (Singulair), a potent cysteinyl leukotriene 1 receptor antagonist, in human plasma and bile. Drug Metab Dispos 25:1282–1287.
  • Ballatori, N. (2005). Biology of a novel organic solute and steroid transporter. OSTalpha-OSTbeta Exp Biol Med 230;689–698.
  • Baltes, E., Coupez, R., Giezek, H., Voss, G., Meyerhoff, C., Strolin Benedetti, M. (2001). Absorption and disposition of levocetirizine, the eutomer of cetirizine, administered alone or as cetirizine to healthy volunteers. Fundam Clin Pharmacol 15:269–277.
  • Behl, C.R., Pimplaskar, H.K., Sileno, A.P., deMeireles, J., Romeo, V.D. (1998). Effects of physicochemical properties and other factors on systemic nasal drug delivery. Adv Drug Del Rev 29:89–116.
  • Beringer, P.M., Slaughter, R.L. (2005). Transporters and their impact on drug disposition. Ann Pharmacother 39:1097–1108.
  • Bertelsen, K.M., Venkatakrishnan, K., von Moltke, L.L., Scott Obach, R., Greenblatt, D.J. (2003). Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: comparison with fluoxetine and quinidine. Drug Metab Dispos 31:289–293.
  • Beyer, K.H., Russo, H.F., Tillson, E.K., Miller, A.K., Verwey, W.F., Gass, S.R. (1951). “Benemid” p-(di-n-pro-pylsulfamyl)- benzoic acid: its renal affinity and its elimination. Am J Physiol 166:625–640.
  • Bielory, L., Leonov, A. (2008). Stereoconfiguration of antiallergic and immunologic drugs. Ann Allergy Asthma Immunol 100:1–9.
  • Boomer, (2008). Available at: http://www.boomer.org/c/p1/Ch16/Ch1602.html.
  • Bourne, D. (2008a). A first course in pharmacokinetics and biopharmaceutics. http://www.boomer.org/c/p1/ch16/Ch1602.html. Access date May 19 2009.
  • Bourne, D. (2008b). A first course in pharmacokinetics and biopharmaceutics. http://www.boomer.org/c/p1/ch16/Ch1603.html. Access date May 19 2009.
  • Bourne, D. (2008c). A first course in pharmacokinetics and biopharmaceutics. http://www.boomer.org/c/p1/Ch18/Ch1802.html, accessed October 16,2008.
  • Borchardt, R.T. (1990). Assessment of transport barriers using cell and tissue culture systems. Drug Dev Ind Pharm 16:2595–2612.
  • Borst, P., de Wolf, C., van de Wetering, K. (2007). Multidrug resistance-associated proteins 3, 4, and 5. Pflugers Arch 453:661–673.
  • Borst, P., Elferink, R.O. (2002). Mammalian ABC transporters in health and disease. Annu Rev Biochem 71:537–592.
  • Boukouvala, S., Fakis, G. (2005). Arylamine N-acetyltransferases: what we learn from genes and genomes. Drug Metab Rev 37:511–564.
  • Bow, D.A., Perry, J.L., Simon, J.D., Pritchard, J.B. (2006). The impact of plasma protein binding on the renal transport of organic anions. J Pharmacol Exp Ther 316:349–355.
  • Brechue, W.F., Maren, T.H. (1993). pH and drug ionization affects ocular pressure lowering of topical carbonic anhydrase inhibitors. Invest Ophthalmol Vis Sci 34:2581–2587.
  • Brée, F., Thiault, L., Gautiers, G., Strolin Benedetti, M., Baltes, E., Rihoux, J.P., et al. (2002). Blood distribution of levocetirizine, a new nonsedating histamine H1-receptor antagonist, in humans. Fund Clin Pharmacol 16:471–478.
  • Brockton, N., Little, J., Sharp, L., Cotton, S.C. (2000). N-acetyltransferase polymorphisms and colorectal cancer. Am J Epidemiol 151:846–861.
  • Caldwell, J. (2001). Do single enantiomers have something special to offer? Hum Psychopharmacol Clin Exp 16:S67–S71.
  • Canal, P., Sqalli, A., de Forni, M., Chevreau, C., Pujol, A., Bugat, R., et al. (1991). Chronopharmacokinetics of doxorubicin in patients with breast cancer. Eur J Clin Pharmacol 40:287–291.
  • Chang, S.C., Bundgaard, H., Buur, A., Lee, V.H.L. (1987). Improved corneal penetration of timolol by prodrugs as a mean to reduce systemic drug load. Invest Ophthalmol Vis Sci 28:487–491.
  • Chaufour, S., Caplain, H., Lilienthal, N., L’héritier, C., Deschamps, C., Dubruc, C., et al. (1999). Study of cardiac repolarization in healthy volunteers performed with mizolastine, a new H1-receptor antagonist. Br J Clin Pharmacol 47:515–520.
  • Chemuturi, N.V., Donovan, M.D. (2007). Role of organic cation transporters in dopamine uptake across olfactory and nasal respiratory tissues. Mol Pharm 4:936–942.
  • Chen, C. (2007). Some pharmacokinetic aspects of the lipophilic terfenadine and zwitterionic fexofenadine in humans. Drugs R D 8:301–314.
  • Chiba, M., Xu, X., Nishime, J.A., Balani, S.K., Lin, J.H. (1997). Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans. Drug Metab Dispos 25:1022–1031.
  • Chien, D-S., Sasaki, H., Bundgaard, H., Buur, A., Lee, VHL. (1991). Role of enzymatic lability in the corneal and conjunctival penetration of timolol ester prodrugs in the pigmented rabbit. Pharm Res 8:728–733.
  • Chrai, S.S., Patton, T.F., Mehta, A., Robinson, J.R. (1973). Lacrimal and instilled fluid dynamics in rabbit eyes. J Pharm Sci 62:1112–1121.
  • Ciarimboli, G. (2008). Organic cation transporters. Xenobiotica 38:936–971.
  • Colice, G.L. (2006). New developments in inhaled corticosteroids. Allergy Asthma Proc 27:332–340.
  • Cooray, H.C., Shahi, S., Cahn, A.P., van Veen, H.W., Hladky, S.B., et al. (2006). Modulation of P-glycoprotein and breast cancer resistance protein by some prescribed corticosteroids. Eur J Pharmacol 531:25–33.
  • Cordon-Cardo, C., O’Brien, J.P., Casals, D., Rittman, G.L., Biedler, J.L., Melamed, M.R., et al. (1989). Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci 86:695–698.
  • Costantino, H.R., Illum, L., Brandt, G., Johnson, P.H., Quay, S.C. (2007). Intranasal delivery: physicochemical and therapeutic aspects. Int J Pharm 337:1–24.
  • Crampton, H.J. (2002). A comparison of the relative clinical efficacy of a single dose of ketotifen fumarate 0.025% ophthalmic solution versus placebo in inhibiting the signs and symptoms of allergic rhinoconjunctivitis as induced by the conjunctival allergen challenge model. Clin Ther 24:1800–1808.
  • Cvetkovic, M., Leake, B., Fromm, M.F., Wilkinson, G.R., Kim, R.B. (1999). OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos 27:866–871.
  • Davies, A.J., Harinda, V., McEwan, A., Ghose, R.R. (1989). Cardiotoxic effect with convulsions in terfenadine overdose. BMJ 298:325.
  • de Boer, A.G., van der Sandt, I.C.J., Gaillard, P.J. (2003). The role of drug transporters at the blood-brain barrier. Annu Rev Pharmacol Toxicol 43:629–656.
  • Dechant, K.L., Goa, K.L. (1991). Levocabastine: a review of its pharmacosuspension properties and therapeutic potential as a topical antihistamine in allergic rhinitis and conjunctivitis. Drugs 41:202–224.
  • Dekhuijzen, P.N., Koopmans, P.P. (2002). Pharmacokinetic profile of zafirlukast. Clin Pharmacokinet 41:105–114.
  • Del Amo, E.M., Urtti, A. (2008). Current and future ophthalmic drug delivery systems: a shift to the posterior segment. Drug Discov Today 13:135–143.
  • Derendorf, H. (2005). Corticosteroid pharmacokinetic/pharmacodynamic parameters and their relationship to safety and efficacy. Allergy Asthma Proc 26:327–335.
  • Derendorf, H., Meltzer, E.O. (2008). Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications. Allergy 63:1292–1300.
  • Dilger, K., Schwab, M., Fromm, M.F. (2004). Identification of budesonide and prednisone as substrates of the intestinal drug efflux pump P-glycoprotein. Inflamm Bowel Dis 10:578–583.
  • Ding, X., Dahl, A.R. (2003). lfactory mucosa:composition, enzymatic localization, and metabolism. In: Doty, R.L. (Ed.), Handbook of Olfaction and Gustation, 2nd ed. (pp 51–73 ). New York: Marcel Dekker.
  • Ding, X., Kaminski, L.S. (2003). Human extrahepatic cytochrome P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annu Rev Pharmacol Toxicol 43:149–173.
  • Draggan, S., Monosson, E. (Topic Eds.). (2007). Excretion of toxicants. In: Cleveland, C.J. (Ed.), Encyclopedia of Earth. Washington, DC: Environmental Information Coalition, National Council for Science and the Environment. [First published in the Encyclopedia of Earth November 28, 2006; Last revised February 8, 2007]. http://www.eoearth.org/article/Excretion_of_toxicants. Accessed May 19, 2009.
  • Drettner, B. (1979). The role of the nose in the functional unit of the respiratory system. Rhynology 17:3–11.
  • Ekaratanawong, S., Anzai, N., Jutabha, P., Miyazaki, H., Noshiro, R., Takeda, M., et al. (2004). Human organic anion transporter 4 is a renal apical organic anion/dicarboxylate exchanger in the proximal tubules. J Pharmacol Sci 94:297–304.
  • El-Sheikh, A.A., Masereeuw, R., Russel, F.G. (2008). Mechanisms of renal anionic drug transport. Eur J Pharmacol 585:245–255.
  • Etienne-Grimaldi, M-C., Cardot, J-M., François, E., Renée, N., Douillard, J-Y., Gamelin, E., et al. (2008). Chronopharmacokinetics of oral tegafur and uracil in colorectal cancer patients. Clin Pharmacol Ther 83:413–415.
  • European Medicines Agency. (2004). Position Paper on Non-Clinical Safety Studies to Support Clinical Studys with a Single Microdose CPMP/SWP/2599/02/Rev1. Available at: http://www.emea.eu.int/pdfs/human/swp/259902en.pdf. May 18, 2009 accessed.
  • European Union Microdosing AMS Partnership Programme (EUMAPP). Background Paper (2006). Available at: www.eumapp.com, access date 18 May, 2009.
  • FDA Guidance for Industry: Exploratory IND Studies. (January 2006). Available at: www.fda.gov/cder/guidance/7086fnl.htm. Access date May 19, 2009.
  • Fears, R., Baggaley, K.H., Alexander, R., Morgan, B., Hindley, R.M. (1978). The participation of ethyl 4-benzyloxybenzoate (BRL 10894) and other aryl-substituted acids in glycerolipid metabolism. J Lipid Res 19:3–11.
  • Feldmann, R.J., Maibach, H.I. (1967). Region variation in percutaneous penetration of 14C cortisol in man. J Invest Dermatol 48:181–183.
  • Fisher, M.B., Paine, M.F., Strelevitz, T.J., Wrighton, S.A. (2001). The role of hepatic and extrahepatic UDP-glucuronosyltransferases in human drug metabolism. Drug Metab Rev 33:273–297.
  • Foster, R.T., Jamali, F. (1988). Stereoselective pharmacokinetics of ketoprofen in the rat. Influence of route of administration. Drug Metab Dispos 16:623–626.
  • Foster, R.T., Jamali, F., Russell, A.S., Alballa, S.R. (1988). Pharmacokinetics of ketoprofen enantiomers in healthy subjects following single and multiple doses. J Pharm Sci 77:70–73.
  • Fretland, A.J., Omiecinski, C.J. (2000). Epoxide hydrolases: biochemistry and molecular biology. Chem Biol Interact 129:41–59.
  • Friedrich, S.W., Cheng, Y-L., Saville, B.A. (1993). Theoretical corneal permeation model for ionizable drugs. J Ocul Pharmacol Ther 9:229–249.
  • Friesen, C.A., Kearns, G.L., Andre, L., Neustrom, M., Roberts, C.C., Abdel-Rahman, S.M. (2004). Clinical efficacy and pharmacokinetics of montelukast in dyspeptic children with duodenal eosinophilia. J Ped Gastroenterol Nutr 38:343–351.
  • Funk, C. (2008). The role of hepatic transporters in drug elimination. Expert Opin Drug Metab Toxicol 4:363–379.
  • Ghibellini, G., Leslie, E.M., Brouwer, K.L. (2006a). Methods to evaluate biliary excretion of drugs in humans: an updated review. Mol Pharm 3:198–211.
  • Ghibellini, G., Vasist, L.S., Hill, T.E., Heizer, W.D., Kowalsky, R.J., Brouwer, K.L. (2006b). Determination of the biliary excretion of piperacillin in humans using a novel method. Br J Clin Pharmacol 62:304–308.
  • Ghosal, A., Yuan, Y., Hapangama, N., Su, A.D., Alvarez, N., Chowdhury, S.K., et al. (2004). Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of 3-hydroxydesloratadine. Biopharm Drug Dispos 25:243–252.
  • Giacomini, K.M., Nelson, W.L., Pershe, R.A., Valdivieso, L., Turner-Tamiyasu, K., Blaschke, T.F. (1986). In vivo interaction of the enantiomers of disopyramide in human subjects. J Pharmacokinet Biopharm 14:335–356.
  • Giacomini, K.M., Sugiyama, Y. (2006) Membrane transporters and drug response. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw-Hill.
  • Gillard, M., Van Der Perren, C., Moguilevsky, N., Massingham, R., Chatelain, P. (2002). Binding characteristics of cetirizine and levocetirizine to human H1 histamine receptors: contribution of Lys191 and Thr194. Mol Pharmacol 61:391–399.
  • Gillespie, W.R. (1991). Noncompartmental versus compartmental modelling in clinical pharmacokinetics, Clin Pharmacokinet 20:253–262.
  • Glaeser, H., Bailey, D.G., Dresser, G.K., Gregor, J.C., Schwarz, U.I., McGrath, J.S., et al. (2007). Intestinal drug transporter expression and the impact of grapefruit juice in humans. Clin Pharmacol Ther 81:362–370.
  • Goldsmith, L.A. (Ed.). (1991). Physiology, Biochemistry, and Molecular Biology of the Skin. New York: Oxford University Press.
  • Gonzales, F.J., Tukey, R.H. (2005). Drug metabolism. In: Brunton, L.L., Lazo, J.S., Parker, K.L., (Eds.), Goodman and Gilman’s the Pharmacological Basis of Therapeutics. McGraw-Hill, New York, United States.
  • Grant, J.A., Riethuisen, J.M., Moulaert, B., De Vos, C. (2002). A double- blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects. Ann Allergy Asthma Immunol 88:190–197.
  • Grass, G.M., Robinson, J.R. (1988). Mechanisms of corneal drug penetration II: ultrastructural analysis of potential pathways for drug movement. J Pharm Sci 77:15–23.
  • Gurny, R., Ibrahim, H., Aebi, A., Buri, P., Wilson, C.G., Washington, N., et al. (1987). Design and evaluation of controlled release systems for the eye. J Contr Rel 6:367–373.
  • Hagenbuch, B., Gui, C. (2008). Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica 38:778–801.
  • Hague, D., Smith, R.L. (1988). Enigmatic properties of (+)-thalidomide; an example of a stable racemic compound. Br.J Clin Pharmacol 26:632P.
  • Haria, M., Fitton, A., Peters, D.H. (1994). Loratadine A. Drugs 48:617–637.
  • Hashizume, T., Imaoka, S., Mise, M., Terauchi, Y., Fujii, T., Miyazaki, H., et al. (2002). Involvement of CYP2J2 and CYP4F12 in the metabolism of ebastine in human intestinal microsomes. J Pharmacol Exp Ther 300:298–304.
  • Haye, R., Hoye, K., Berg, O., Frones, S., Odegard, T. (2005). Morning versus evening dosing of desloratadine in seasonal allergic rhinitis: a randomized, controlled study. Clin Mol Allergy 3:1–6.
  • Herman, H. (2007). Once-daily administration of intranasal corticosteroids for allergic rhinitis: a comparative review of efficacy, safety, patient preference, and cost. Am J Physiol 21:70–79.
  • Hey, J.A., del Prado, M., Kreutner, W., Egan, R.W. (1996). Cardiotoxic and drug interaction profile of the second-generation antihistamines ebastine and terfenadine in an experimental animal model of torsade de pointes. Arzneimittelforschung 46:159–163.
  • Heykants, J., Van Peer, A., Van de Velde, V., Snoeck, E., Meuldermans, W., Woestenborghs, R. (1995). The pharmacokinetic properties of topical levocabastine. A review. Clin Pharmacokinet 29:221–230.
  • Hla, K.K., Latham, A.N., Henry, J.A. (1992). Influence of time of administration on verapamil pharmacokinetics. Clin Pharmacol Ther 51:366–370.
  • Ho, R.H., Kim, R.B. (2005). Transporters and drug therapy: implications for drug disposition and disease. Clin Pharmacol Ther 78:260–277.
  • Hochhaus, G. (2008). Pharmacokinetic/pharmacodynamic profile of mometasone furoate nasal spray: potential effects on clinical safety and efficacy. Clin Ther 30:1–13.
  • Hsyu, P-H., Giacomini, K.M. (1985). Stereoselective renal clearance of pindolol in humans. J Clin Invest 76:1720–1726.
  • Huang, A.J.W., Tseng, S.C.G., Kenyon, K.R. (1989). Paracellular permeability of corneal and conjunctival epithelia. Invest Ophthalmol Vis Sci 30:684–689.
  • Hughes, S.C., Shardlow, P.C., Hollis, F.J., Scott, R.J., Motivaras, D.S., Allen, A., et al. (2008). Metabolism and disposition of fluticasone furoate, an enhanced-affinity glucocorticoid, in humans. Drug Metab Dispos 36:2337–2344.
  • Hutt, A.J., Caldwell, J. (1983). The metabolic chiral inversion of 2- arylpropionic acids—a novel route with pharmacological consequences. J Pharm Pharmacol 35:693–704.
  • Ibiapina, C.C., Sarinho, E.S.C., Camargos, P.A.M., de Andrade, C.R., da Cruz Filho, A.A.S. (2008). Allergic rhinitis: epidemiological aspects, diagnosis, and treatment. J Bras Pneumol 34:230–240.
  • Illum, L., (2003). Nasal drug delivery—possibilities, problems, and solutions. J Contr Rel 87:187–198.
  • Inui, K.I., Masuda, S., Saito, H. (2000). Cellular and molecular aspects of drug transport in the kidney. Kidney Int 58:944–958.
  • Ishiguro, N., Nozawa, T., Tsujihata, A., Saito, A., Kishimoto, W., Yokoyama, K., et al. (2004). Influx and efflux transport of H1-antagonist epinastine across the blood-brain barrier. Drug Metab Dispos 32:519–524.
  • Ishikawa, T. (1992). The ATP-dependent glutathione S-conjugate export pump. Trends Biochem Sci 17:463–468.
  • Jamali, F. (1988). Pharmacokinetics of enantiomers of chiral nonsteroidal anti-inflammatory drugs. Eur J Drug Metab Pharmacokinet 13:1–9.
  • Johnson, W.W. (2008). Cytochrome P450 inactivation by pharmaceuticals and phytochemicals: therapeutic relevance. Drug Metabol Rev 40:101–147.
  • Kaiser, H.B., Naclerio, R.M., John Given, J., Toler, T.N., Ellsworth, A., Philpot, E.E. (2007). Fluticasone furoate nasal spray: a single treatment option for the symptoms of seasonal allergic rhinitis. J Allergy Clin Immunol 119:1430–1437.
  • Kaliner, M.A. (2006). Pharmacologic characteristics and adrenal suppression with newer inhaled corticosteroids: a comparison of ciclesonide and fluticasone propionate. Clin Ther 28:319–331.
  • Kappus, H. (1986). Overview of enzyme systems involved in bioreduction of drugs and in redox cycling. Biochem Pharmacol 35:1–6.
  • Kassahun, K., Skordos, K., McIntosh, I., Slaughter, D., Doss, G.A., Baillie, T.A., et al. (2005). Zafirlukast metabolism by cytochrome P450 3A4 produces an electrophilic α,β-unsaturated iminium species that results in the selective mechanism-based inactivation of the enzyme. Chem Res Toxicol 18:1427–1437.
  • Keister, J.C., Cooper, E.R., Missel, P.J., Lang, J.C., Hager, D.F. (1991). Limits on optimizing ocular drug delivery. J Pharm Sci 80:50–53.
  • Kim, K.A., Park, P.W., Park, J.Y., Short-term effect of quercetin on the pharmacokinetics of fexofenadine, a substrate of P-glycoprotein, in healthy volunteers. Eur J Clin Pharmacol. http://www.Springerlink.com/content/t0p75t3123899411/?p=b4a4decfb7114ccb9930e917b61ddbe5&pi=2, Accessed May 18, 2009.
  • Koepsell, H., Lips, K., Volk, C. (2007). Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res 24:1227–1251.
  • Koshiba, S., An, R., Saito, H., Wakabayashi, K., Tamura, A., Ishikawa, T. (2008). Human ABC transporters ABCG2 (BCRP) and ABCG4. Xenobiotica 38:863–888.
  • Kullak-Ublick, G.A., Stieger, B., Meier, P.J. (2004). Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 126:322–342.
  • Labaune, J.P. (1989). Handbook of Pharmacokinetics, Toxicity Assessment of Chemicals. Ellis Horwood Limited, Chichester, England (pp 345–348 ).
  • Lacy, S.A., Hitchcock, M.J., Lee, W.A., Tellier, P., Cundy, K.C. (1998). Effect of oral probenecid coadministration on the chronic toxicity and pharmacokinetics of intravenous cidofovir in cynomolgus monkeys. Toxicol Sci 44:97–106.
  • Lamiable, D., Vistelle, R., Fay, R., Millart, H., Caron, J., Choisy, H. (1991). Dexamethasone chronopharmacokinetics in young subjects. Therapie 46:405–407.
  • Lappin, G., Garner, R.C. (2003) Big physics, small doses—the use of AMS and PET in human microdosing of development drugs. Nat Rev (Drug Discov) 2:233–240.
  • Lappin, G., Garner, R.C. (2006). A review of human phase 0 (microdosing) clinical trials following the U.S. Food and Drug Administration exploratory investigational new drug studies guidance. Int J Pharm Med 20:159–165.
  • Lappin, G., Kuhnz, W., Jochemsen, R., Kneer, J., Chaudhary, A., Oosterhuis, B., et al. (2006). Use of microdosing to predict pharmacokinetics at the therapeutic dose: experience with five drugs. Clin Pharmacol Ther 80:203–215.
  • Larsen, B.T., Gutterman, D.D., Hatoum, O.A. (2006). Emerging role of epoxyeicosatrienoic acids in coronary vascular function. Eur J Clin Invest 36:293–300.
  • Launay-Vacher, V., Izzedine, H., Karie, S., Hulot, J.S., Baumelou, A., Deray, G. (2006). Renal tubular drug transporters. Nephron Physiol 103:97–106.
  • Le Corre, P., Gibassier, D., Sado, P., Le Verge, R. (1988). Stereoselective metabolism and pharmacokinetics of disopyramide enantiomers in humans. Drug Metab Dispos 16:858–864.
  • Lebrun-Vignes, B., Diquet, B., Chosidow, O. (2001). Clinical pharmacokinetics of mizolastine. Clin Pharmacokinet 40:501–507.
  • Lechapt-Zalcman, E., Hurbain, I., Lacave, R., Commo, F., Urban, T., Antoine, M., et al. (1997). MDR1-Pgp 170 expression in human bronchus. Eur Respir J 10:1837–1843.
  • Lecureur, V., Courtois, A., Payen, L., Verhnet, L., Guillouzo, A., Fardel, O. (2000). Expression and regulation of hepatic drug and bile acid transporters. Toxicology 153:203–219.
  • Lederer, C.M., Jr, Harold, R.E. (1986). Drop size of commercial glaucoma medications. Am J Ophthalmol 101:691–694.
  • Lee, E.J.D., Williams, K.M. (1990). Chirality. Clinical pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet 18:339–345.
  • Lee, V.H.L., Robinson, J.R. (1979). Mechanistic and quantitative evaluation of precorneal pilocarpine disposition in albino rabbits. J Pharm Sci 68:673–684.
  • Lee, Y-H., Kompella, I.J.B., Lee, VHL. (1993). Systemic absorption pathways of topically applied beta adrenergic antagonists in the pigmented rabbit. Exp Eye Res 57:341–349.
  • Legler, U.F., Benet, L.Z. (1986). The effect of prednisone and hydrocortisone on the plasma protein binding of prednisolone in man. Eur J Clin Pharmacol 30:51–55.
  • Lennard, M.S., Tucker, G.T., Silas, J.H. (1983). Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquin metabolizers. Clin Pharmacol Ther 34:732.
  • Leonov, A., Bielory, L. (2007). Chirality in ocular agents. Curr Opin Allergy Clin Immunol 7:418–423.
  • Li, M., Anderson, G.D., Wang, J. (2006). Drug-drug interactions involving membrane transporters in the human kidney. Expert Opin Drug Metab Toxicol 2:505–532.
  • Liaw, J., Rojanasakul, Y., Robinson, J.R. (1992). The effect of drug charge type and charge density on corneal transport. Int J Pharm 88:111–124.
  • Lima, J.J., Boudoulas, H., Shields, B. (1985). Stereoselective pharmacokinetics of disopyramide enantiomers in man. Drug Metab Dispos 13:572–577.
  • Lin, J.H. (2006). Tissue distribution and pharmacodynamics: a complicated relationship. Curr Drug Metab 7:39–65.
  • Lindsay, J., Wang, L.L., Li, Y., Zhou, S.F. (2008). Structure, function, and polymorphism of human cytosolic sulfotransferases. Curr Drug Metab 9:99–105.
  • Lippert, C., Ling, J., Brown, P., Burmaster, S. (1995). Mass balance and pharmacokinetics of MDL 16455A in healthy, male volunteers. Pharmacol Res (NY) 12:S390.
  • Liu, L., Cheng, H., Zhao, J.J., Rogers, J.D. (1997). Determination of montelukast (MK-0476) and its S-enantiomer in human plasma by stereoselective high-performance liquid chromatography with column-switching. J Pharm Biomed Anal 15:631–638.
  • Löscher, W., Potschka, H. (2005). Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases. Prog Neurobiol 76:22–76.
  • Ludwig, A., Van Ooteghem, M. (1989). The evaluation of viscous ophthalmic vehicles by slit lamp fluorophotometry in humans. Int J Pharm 54:95–102.
  • Lumry, W.R. (1999). A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis. J Allergy Clin Immunol 104:S150–S158.
  • Mahar Doan, K.M., Wring, S.A., Shampine, L.J., Jordan, K.H., Bishop, J.P., Kratz, J., et al. (2004). Steady-state brain concentrations of antihistamines in rats: interplay of membrane permeability, P-glycoprotein efflux, and plasma protein binding. Pharmacology 72:92–98.
  • Maier, A., Zimmermann, C., Beglinger, C., Drewe, J., Gutmann, H. (2007). Effects of budesonide on P-glycoprotein expression in intestinal cell lines. Br J Pharmacol 150:361–368.
  • Marshall, E.K., Vickers, L. (1923). The mechanism of the elimination of phenolsulphonphtalein by kidney—a proof of secretion by the convoluted tubules. Bull Johns Hopkins Hosp 34:1–6.
  • Martin, L.E., Harrison, C., Tanner, R.J. (1975). Metabolism of beclomethasone dipropionate by animals and man. Postgrad Med J 51:11–20.
  • Masuda, S., Terada, T., Yonezawa, A., Tanihara, Y., Kishimoto, K., Katsura, T., et al. (2006). Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug, and toxin extrusion 2. J Am Soc Nephrol 17:2127–2135.
  • Matsushima, S., Maeda, K., Hayashi, H., Debori, Y., Schinkel, A.H., Schuetz, J.D., et al. (2008a). Involvement of multiple efflux transporters in hepatic disposition of fexofenadine. Mol Pharmacol 73:1474–1483.
  • Matsushima, S., Maeda, K., Inoue, K., Ohta, K.Y., Yuasa, H., Kondo, T., et al. (2008b). The inhibition of human multidrug and toxin extrusion 1 (hMATE1) is involved in the drug-drug interaction caused by cimetidine. Drug Metab Dispos 2008 Dec 12. [Epub ahead of print].
  • Matsushima, S., Maeda, K., Ishiguro, N., Igarashi, T., Sugiyama, Y. (2008c). Investigation of the inhibitory effects of various drugs on the hepatic uptake of fexofenadine in humans. Drug Metab Dispos 36:663–669.
  • Matzke, G.R., Yeh, J., Awni, W.M., Halstenson, C.E., Chung, M. (1987). Pharmacokinetics of cetirizine in the elderly and patients with renal insufficiency. Ann Allergy 59:25–30.
  • Meseguer, G., Gurny, R., Buri, P., Rozier, A., Plazonnet, B. (1993). Gamma scintigraphic study of precorneal drainage and assessment of miotic response in rabbits of various ophthalmic formulations containing pilocarpine. Int J Pharm 95:229–234.
  • Mesnil, F., Dubruc, C., Mentre, F., Huet, S., Mallet, A., Thenot, J.P. (1997). Pharmacokinetic analysis of mizolastine in healthy young volunteers after single oral and intravenous doses: noncompartmental approach and compartmental modeling. J Pharmacokinet Biopharm 25:125–147.
  • Mimura, N., Nagata, Y., Kuwabara, T., Kubo, N., Fuse, E. (2008). P-glycoprotein limits the brain penetration of olopatadine hydrochloride, H1-receptor antagonist. Drug Metab Pharmacokinet 23:106–114.
  • Miura, M., Uno, T., Tateishi, T., Suzuki, T. (2007). Pharmacokinetics of fexofenadine enantiomers in healthy subjects. Chirality 19:223–227.
  • Molimard, M., Diquet, B., Strolin Benedetti, M. (2004). Comparison of pharmacokinetics and metabolism of desloratadine, fexofenadine, levocetirizine, and mizolastine in humans. Fundam Clin Pharmacol 18:399–411.
  • Moriyama, Y., Hiasa, M., Matsumoto, T., Omote, H. (2008). Multidrug and toxic compound extrusion (MATE)-type proteins as anchor transporters for the excretion of metabolic waste products and xenobiotics. Xenobiotica 38:1107–1118.
  • Mortimer, K.J., Harrison, T.W., Tang, Y., Wu, K., Lewis, S., Sahasranaman, S., et al. (2006). Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma. Br J Clin Pharmacol 62:412–419.
  • Mougey, E.B., Feng, H., Castro, M., Irvin, C.G., Lima, J.J. (2009). Absorption of montelukast is transporter mediated: a common variant of OATP2B1 is associated with reduced plasma concentrations and poor response. Pharmacogenet Genomics 19:129–138.
  • Nadendla, R.R. (2004). Principles of Organic Medicinal Chemistry. New Delhi, India: New Age International Limited.
  • Nakamura, Y., Yamaguchi, T., Takahashi, S., Hashimoto, S., Iwatani, K., Nagagawa, Y. (1981). Optical isomerization mechanism of R(-)-hydratropic acid derivatives. J Pharmacobiol Dynamics 4:S1.
  • Nave, R., Bethke, T.D., van Marle, S.P., Zech, K. (2004). Pharmacokinetics of [14C] ciclesonide after oral and intravenous administration to healthy subjects. Clin Pharmacokinet 43:479–486.
  • Nave, R., Meyer, W., Fuhst, R., Zech, K. (2005). Formation of fatty acid conjugates of ciclesonide active metabolite in the rat lung after 4-week inhalation of ciclesonide. Pulm Pharmacol Ther 18:390–396.
  • Newell, F.W. (1986). Ophthalmology, Principles and Concepts, 6th ed. St. Louis, Missouri, USA: C.V Mosby.
  • Notterman, D.A., Drayer, D.E., Metakis, L., Reidenberg, M.M. (1986). Stereoselective renal tubular secretion of quinidine and quinine. Clin Pharmacol Ther 40:511–517.
  • Obradovic, T., Dobson, G.G., Shingaki, T., Kungu, T., Hidalgo, I.J. (2008). Assessment of the first- and second-generation antihistamines brain penetration and role of P-glycoprotein. Pharm Res 24:318–327.
  • Ofori-Adjei, D., Ericsson, O., Lindstrom, B., Hermansson, J., Adjepon-Yamoah, K., Sjoqvist, F. (1986). Enantioselective anamysis of chloroquine and desethylchloroquine after oral administration of racemic chloroquine. Ther Drug Monit 8:457–461.
  • Ohashi, R., Kamikozawa, Y., Sugiura, M., Fukuda, H., Yabuuchi, H., Tamai, I. (2006). Effect of P-glycoprotein on intestinal absorption and brain penetration of antiallergic agent bepotastine besilate. Drug Metab Dispos 34:793–799.
  • Ohta, K.Y., Inoue, K., Hayashi, Y., Yuasa, H. (2006). Molecular identification and functional characterization of rat multidrug and toxin extrusion-type transporter 1 as an organic cation/H+ antiporter in the kidney. Drug Metab Dispos 34:1868–1874.
  • Paul, H.B., Welte, T., Groneberg, D.A. (2005). Drug transport in the respiratory epithelium. Pneumologie 59:461–469.
  • Pearce, R.E., Leeder, J.S., Kearns, G.L. (2006). Biotransformation of fluticasone: in vitro characterization. DrugMetab Dispos 34:1035–1040.
  • Polli, J.W., Baughman, T.M., Humphreys, J.E., Jordan, K.H., Mote, A.L., Salisbury, J.A., et al. (2003). P-glycoprotein influences the brain concentrations of Cetirizine (Zyrtec®), a second-generation nonsedating antihistamine. J Pharm Sci 92:2082–2089.
  • Polli, J.W., Wring, S.A., Humphreys, J.E., Huang, L., Morgan, J.B., Webster, L.O., et al. (2001). Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther 299:620–628.
  • Polonikov, A.V., Ivanov, V.P., Solodilova, M.A., Khoroshaya, I.V., Kozhuhov, M.A., Panfilov, V.I. (2007). Promoter polymorphism G-50T of a human CYP2J2 epoxygenase gene is associated with common susceptibility to asthma. Chest 132:120–126.
  • Poondru, S., Devaraj, R., Boinpally, R.R., Yamasani, M.R. (2000). Chronopharmacokinetics of sumatriptan in healthy human subjects. J Pharm Pharmacol 52:1085–1090.
  • Poulin, P., Theil, F-P. (2002). Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution. J Pharm Sci 91:129–156.
  • Prenner, B., Kim, K., Gupta, S., Khalilieh, S., Kantesaria, B., Manitpisitkul, P., et al. (2006). Adult and paediatric poor metabolisers of desloratadine: an assessment of pharmacokinetics and safety. Expert Opin Drug Saf 5:211–223.
  • Riethmuller-Winzen, H., Peter, G., Buker, K.M. (1994). Tolerability, pharmacokinetics, and dose linearity of azelastine hydrochloride in healthy subjects. Arzneimittel Forschung 44:1136–1140.
  • Rimmer, S.J., Church, M.K. (1990). The pharmacology and mechanisms of action of histamine H1-antagonists. Clin Exp Allergy 20:3–17.
  • Rius, M., Hummel-Eisenbeiss, J., Keppler, D. (2008). ATP-dependent transport of leukotrienes B4 and C4 by the multidrug resistance protein ABCC4 (MRP4). J Pharmacol Exp Ther 324:86–94.
  • Rius, M., Nies, A.T., Hummel-Eisenbeiss, J., Jedlitschky, G., Keppler, D. (2003). Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology 38:374–384.
  • Robbins, D.K., Castles, M.A., Pack, D.J., Bhargava, V.O., Weir, S.J. (1998). Dose proportionality and comparison of single- and multiple-dose pharmacokinetics of fexofenadine (MDL 16455) and its enantiomers in healthy male volunteers. Biopharm Drug Dispos 19:455–463.
  • Roberts, M.S., Magnusson, B.M., Burczynski, F.J., Weiss, M. (2002). Enterohepatic circulation: physiological, pharmacokinetic, and clinical implications. Clin Pharmacokinet 41:751–790.
  • Robertson, E.E., Rankin, G.O. (2006). Human renal organic anion transporters: characteristics and contributions to drug and drug metabolite excretion. Pharmacol Ther 109:399–412.
  • Rohatagi, S., Appajosyula, S., Derendorf, H., Szefler, S., Nave, R., Zech, K., et al. (2004). Risk-benefit value of inhaled glucocorticosteroids: a pharmacokinetic/pharmacodynamic perspective. J Clin Pharm 44:37–47.
  • Rohatagi, S., Arya, V., Zech, K., Nave, R., Hochhaus, G., Jensen, B.K., et al. (2003a). Population pharmacokinetics and pharmacodynamics of ciclesonide. J Clin Pharmacol 43:365–378.
  • Rohatagi, S., Bye, A., Falcoz, C., Mackie, A.E., Miebohm, B., Mollmann, H., et al. (1996). Dynamic modeling of cortisol reduction after inhaled administration of fluticasone propionate. J Clin Pharmacol 36:938–941.
  • Rohatagi, S., Derendorf, H., Zech, K., Nave, R., Banerji, D. (2003b). PK/PD of inhaled corticosteroids: the risk/benefit of inhaled ciclesonide. J. Allergy Clin. Immunol 111:S218.
  • Rohatagi, S., Hochhaus, G., Mollmann, H., Barth, J., Galia, E., Erdmann, M., et al. (1995). Pharmacokinetic and pharmacodynamic evaluation of triamcinolone acetonide after intravenous, oral, and inhaled administration. J Clin Pharmacol 35:1187–1193.
  • Rojanasakul, Y., Robinson, J.R. (1989). Transport mechanisms of the cornea: characterization of barrier permselectivity. Int J Pharm 55:237–246.
  • Rojanasakul, Y., Wang, L-Y., Bhat, M., Glover, D.D., Malanga, C.J., Ma, JKH. (1992). The transport barrier of epithelia: a comparative study on membrane permeability and charge selectivity in the rabbit. Pharm Res 9:1029–1034.
  • Rollins, D.E., Klaassen, C.D. (1979). Biliary excretion of drugs in man. Clin Pharmacokinet 4:368–379.
  • Rowland, M., Tozer, T.N. (1995a). Distribution. In: Rowland M. and Tozer TN (Ed.), Clinical Pharmacokinetics—Concepts and Applications, 3rd ed. (pp 137–155 ). Media, Pennsylvania, USA: Williams & Wilkins.
  • Rowland, M., Tozer, T.N. (1995b). Turnover concepts. In: Rowland, M., Tozer, T.N. (Ed.), Clinical Pharmacokinetics—Concepts and Applications, 3rd ed. (pp 424–442 ). Media, Pennsylvania, USA: Williams & Wilkins.
  • Rowland, M., Tozer, T.N. (1995c). Basic considerations. In: Rowland, M., Tozer, T.N. (Ed.), Clinical Pharmacokinetics—Concepts and Applications, 3rd ed. (pp 11–17 ). Media, Pennsylvania, USA: Williams & Wilkins.
  • Rubio-Aliaga, I., Daniel, H. (2008). Peptide transporters and their roles in physiological processes and drug disposition. Xenobiotica 38:1022–1042.
  • Saito, K., Yamazoe, Y., Kamataki, T., Kato, R. (1984). Glutathione transferase-mediated and nonenzymatic activation and detoxication of the N-hydroxy derivative of Trp-P-2, a potent pyrolysate promutagen. Xenobiotica 14:545–548.
  • Salib, R.J., Howarth, P.H. (2003). Safety and tolerability profiles of intranasal antihistamines and intranasal corticosteroids in the treatment of allergic rhinitis. Drug Saf 26:863–893.
  • Savidge, R.D., Bui, K.H., Birmingham, B.K., Morse, J.L., Spreen, R.C. (1998). Metabolism and excretion of zafirlukast in dogs, rats, and mice. Drug Metab Dispos 26:1069–1076.
  • Sawada, Y., Hanano, M., Sugiyama, Y., Harashima, H., Iga, T. (1984). Prediction of the volume of distribution of basic drugs in human based on data from animals. J Pharmacokinet Biopharm 12:587–596.
  • Schmith, H.W., Goldring, W., Chassis, H. (1938). The measurement of the tubular excretory mass, effective blood flow, and filtration rate in the normal kidney. J Clin. Invest 17:263–278.
  • Schoenwald, R.D., Ward, R. (1978). Relationship between steroid permeability across excised rabbit cornea and octanol-water partition coefficients. J Pharm Sci 67:786–788.
  • Schoenwald, R.D., Huang, H-S. (1983). Corneal penetration behaviour of ß-blocking agents I: physicochemical factors. J Pharm Sci 72:1266–1272.
  • Schrag, M.L., Cui, D., Rushmore, T.H., Shou, M., Ma, B., Rodrigues, A.D. (2004). Sulfotransferase 1E1 is a low km isoform mediating the 3-O-sulfation of ethinyl estradiol. Drug Metab Dispos 32:1299–1303.
  • Schran, H.F., Petryk, L., Chang, C.T., O’Connor, R., Gelbert, M.B. (1996). The pharmacokinetics and bioavailability of clemastine and phenylpropanolamine in single-component and combination formulations. J Clin Pharmacol 36:911–922.
  • Schwarz, U.I., Leake, B.F., Kim, R.B., Whomsley, R., Strolin Benedetti, M. (2006). Role of oatp and oat transporters in levocetirizine cellular uptake. Drug Metab Rev 38:S1. Abstract 367.
  • Sendur, N., Uslu, M. (2005). Action mechanism of antihistamines and the new antihistamines. Curr Med Chem 4:465–475.
  • Sharpe, M., Jarvis, B. (2001). Inhaled mometasone fuorate: a review of its use in adults and adolescents with persistent asthma. Drugs 61:1325–1350.
  • Shen, J., Lee, V.H.L. (2002). Application of epithelial cell culture in drug transport in the respiratory tract. Meth Mol Biol 188: 217–232.
  • Shimizu, M., Uno, T., Sugawara, K., Tateishi, T. (2006). Effects of itraconazole and diltiazem on the pharmacokinetics of fexofenadine, a substrate of P-glycoprotein. Br J Clin Pharmacol 61:538–544.
  • Sieg, J.W., Robinson, J.R. (1977). Vehicle effects on ocular drug bioavailability II: evaluation of pilocarpine. J Pharm Sci 66:1222–1228.
  • Simons, F.E.R. (1999). Mizolastine: antihistaminic activity from preclinical data to clinical evaluation. Clin Exp Allergy 29(Suppl 1):3–8.
  • Simons, F.E.R., Simons, K.J. (1991a). Pharmacokinetic optimisation of histamine H1-receptor antagonist therapy. Clin Pharmacokinet 21:372–393.
  • Simons, F.E.R., Simons, K.J. (1991b) Second-generation H1-receptor antagonists. Ann Allergy 66:5–19.
  • Snyder, S.H., Snowman, A.M. (1987). Receptor effects of ceterizine. Ann Allergy 59:4–8.
  • Srimaroeng, C., Perry, J.L., Pritchard, J.B. (2008). Physiology, structure, and regulation of the cloned organic anion transporters. Xenobiotic 38:889–935.
  • Stanaland, B.E. (2004). Once-daily budesonide aqueous nasal spray for allergic rhinitis: a review. Clin Ther 26:473–492.
  • Storms, W.W. (1996). Clinical studies of the efficacy and tolerability of ebastine 10 or 20 mg once-daily in the treatment of seasonal allergic rhinitis in the US. Drugs 52(Suppl 1):20–25.
  • Storms, W.W. (2004). Pharmacologic approaches to daytime and nighttime symptoms of allergic rhinitis. J Allergy Clin Immunol 114:S146–S153.
  • Strolin Benedetti, M., Efthymiopoulos, C., Sassella, D., Moro, E., Repetto, M. (1990). Autoinduction of rifabutin metabolism in man. Xenobiotica 20:1113–1119.
  • Strolin Benedetti, M., Eschalier, A., Lesage, A., Dordain, G., Rovei, V., Zarifian, E., et al. (1984). Effect of a reversible and selective MAO-A inhibitor (Cimoxatone) on diurnal variation in plasma prolactin level in man. Eur J Clin Pharmacol 26:71–77.
  • Strolin Benedetti, M., Pianezzola, E., Fraier, D., Castelli, M.G., Dostert, P. (1991). Stereoselectivity of idarubicin reduction in various animal species and humans. Xenobiotica 21:473–480.
  • Strolin Benedetti, M., Plisnier, M., Kaise, J., Maier, L., Baltes, E., Arendt, C., et al. (2001). Absorption, distribution, metabolism, and excretion of 14C-levocetirizine, the R enantiomer of cetirizine, in healthy volunteers. Eur J Clin Pharmacol 57:571–582.
  • Strolin Benedetti, M., Whomsley, R., Baltes, E. (2006). Involvement of enzymes other than CYPs in the oxidative metabolism of xenobiotics. Expert Opin Drug Metab Toxicol 2:895–921.
  • Strolin Benedetti, M., Whomsley, R., Canning, M. (2007). Drug metabolism in the paediatric population and in the elderly. Drug Discovery Today. 12: 599–610.
  • Strolin Benedetti, M., Whomsley, R., Mathy, F.-X., Jacques, P., Espie, P., Canning, M. (2008). Stereoselective renal tubular secretion of levocetirizine and dextrocetirizine, the two enantiomers of the H1-antihistamine cetirizine. Fundam Clin Pharmacol 22:19–23.
  • Sugrue, M.F. (1989). The pharmacology of antiglaucoma drugs. Pharmac Ther 43:91–138.
  • Tahara, H., Kusuhara, H., Fuse, E., Sugiyama, Y. (2005). P-glycoprotein plays a major role in the efflux of fexofenadine in the small intestine and blood-brain barrier, but only a limited role in its biliary excretion. Drug Metab Dispos 33:963–968.
  • Tahara, H., Kusuhara, H., Maeda, K., Koepsell, H., Fuse, E., Sugiyama, Y. (2006). Inhibition of oat3-mediated renal uptake as a mechanism for drug-drug interaction between fexofenadine and probenecid. Drug Metab Dispos 34:743–747.
  • Tamai, I., Kido, Y., Yamashita, J., Sai, Y., Tsuji, A. (2000). Blood-brain barrier transport of H1-antagonist ebastine and its metabolite carebastine. J Drug Target 8:383–393.
  • Tannergren, C., Knutson, T., Knutson, L., Lennernas, H. (2003b). The effect of ketoconazole on the in vivo intestinal permeability of fexofenadine using a regional perfusion technique. Br J Clin Pharmacol 55:182–190.
  • Tannergren, C., Petri, N., Knutson, L., Hedeland, M., Bondesson, U., Lennernas, H. (2003a). Multiple transport mechanisms involved in the intestinal absorption and first-pass extraction of fexofenadine. Clin Pharmacol Ther 74:423–436.
  • Tasaka, K., Kamei, C., Izushi, K., Tsujimoto, S., Yoshida, T. (1991). Comparison of pharmacological properties of optical isomers and a racemic mixture of epinastine. Arzneimittelforschung 41:219–223.
  • Tashiro, M., Sakurada, Y., Iwabuchi, K., Mochizuki, H., Kato, M., Aoki, M., et al. (2004). Central effects of fexofenadine and cetirizine. Measurement of psychomotor performance, subjective sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography. J Clin Pharmacol 44:890–900.
  • Tateishi, T., Miura, M., Suzuki, T., Uno, T. (2008). The different effects of itraconazole on the pharmacokinetics of fexofenadine enantiomers. Br J Clin Pharmacol 65:1–8.
  • Tayab, Z.R., Hochhaus, G. (2007). Advances in single-entity inhaled corticosteroid therapy. Allergy Asthma Proc 28:125–135.
  • Terada, T., Inui, K. (2008). Physiological and pharmacokinetic roles of H+/organic cation antiporters (MATE/SLC47A). Biochem Pharmacol 75:1689–1696.
  • Terada, T., Masuda, S., Asaka, J., Tsuda, M., Katsura, T., Inui, K. (2006). Molecular cloning, functional characterization, and tissue distribution of rat H+/organic cation antiporter MATE1. Pharm Res 23:1696–1701.
  • Thum, T., Erpenbeck, V.J., Moeller, J., Hohlfeld, J.M., Krug, N., Borlak, J. (2006). Expression of xenobiotic metabolizing enzymes in different lung compartments of smokers and nonsmokers. Environm. Health Perspect 114:1655–1661.
  • Tillement, J.P. (1995). A low distribution volume as a determinant of efficacy and safety for histamine (H1) antagonists. Allergy 50:12–16.
  • Tillement, J.P., Houin, G., Zini, R., et al. (1984). The binding of drugs to blood plasma macromolecules: recent advances and therapeutic significance. Adv Drug Res 13:60–94.
  • Tillement, J.P., Testa, B., Bree, F. (2003). Compared pharmacological characteristics in humans of racemic cetirizine and levocetirizine, two histamine H1-receptor antagonists. Biochem Pharmacol 66:1123–1126.
  • Tomlinson, R.V., Runkel, R., Chaplin, M.D., Bowen, L., Kanagy, J., Chu, N. (1982). In vitro studies on the binding of cloprednol to human plasma proteins. J Steroid Biochem 16:75–80.
  • Tortora, G.J., Grabowski, S.R. (1996). Principles of Anatomy and Physiology, 8th ed. Mento Park, California, USA: Harper Collins.
  • Townsend, D.M., Tew, K.D. (2003). The role of glutathione-S- transferase in anti-cancer drug resistance. Oncogene 22:7369–7375.
  • Toyoda, Y., Hagiya, Y., Adachi, T., Hoshijima, K., Kuo, M.T., Ishikawa, T. (2008). MRP class of human ATP binding cassette (ABC) transporters: historical background and new research directions. Xenobiotica 38:833–862.
  • Tsuji, A. (2002). Transporter-mediated drug interactions. Drug Metab Pharmacokinet 17:253–274.
  • Ünal, M., Hafiz, G. (2005). The role of antihistamines in the management of allergic rhinitis. Curr Med Chem 4:477–480.
  • Urquhart, B.L., Tirona, R.G., Kim, R.B. (2007). Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs. J Clin Pharmacol 47:566–578.
  • Urtti, A. (1990). Controlled drug delivery devices for experimental ocular studies with timolol 2. Ocular and systemic absorption in rabbits. Int J Pharm 61:241–249.
  • Urtti, A. (2006). Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev 58:1131–1135.
  • Urtti, A., Salminen, L. (1993). Minimizing systemic absorption of topically administered ophthalmic drugs. Surv Ophthalmol 37:435–456.
  • Urtti, A., Salminen, L., Miinalaincn, O. (1985). Systemic absorption of ocular pilocarpine is modified by polymer matrices. Int J Pharm 23:147–161.
  • Van Cauwenberge, P., Sys, L., De Belder, T., Watelet, J.B. (2004). Anatomy and physiology of the nose and paranasal sinuses. Immunol Allergy Clin North Am 24:1–17.
  • Van Cauwenberge, P., Van Hoecke, H. (2005). Management of allergic rhinitis. B-ENT. 1(Suppl 1):45–64.
  • van De Waterbeemd, H., Smith, D.A., Beaumont, K., Walker, D.K. (2001). Property-based design: optimization of drug absorption and pharmacokinetics. J Med Chem 44:1313–1333.
  • van der Deen, M., De Vries, E.G., Timens, W., Scheper, R.J., Timmer-Bosscha, H., Postma, D.S. (2005). ATP-binding cassette (ABC) transporters in normal and pathological lung. Respir Res 6:59.
  • Van Drunen, C., Meltzer, E.O., Bachert, C., Bousquet, J., Fokkens, W.J. (2005). Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and safety of mometasone furoate. Allergy 60:5–19.
  • Vander, A., Sherman, J., Luciano, D. (1998) Human Physiology, 7th ed. Boston, Massachusetts, USA: WCB McGraw-Hill.
  • Venkatakrishnan, K., Obach, R.S. (2005). In vitro–in vivo extrapolation of CYP2D6 inactivation by paroxetine: prediction of nonstationary pharmacokinetics and drug interaction magnitude. Drug Metab Dispos 33:845–852.
  • Walker, J., Howarth, P., Hamilton, I. (1988). A placebo-controlled trial of the therapeutic value of levocabastine eye drops used as required in the treatment of seasonal allergic conjunctivitis. Unpublished report N 62497, Janssen Research Foundation, Beerse.
  • Wang, E.J., Casciano, C.N., Clement, R.P., Johnson, W.W. (2001). Evaluation of the interaction of loratadine and desloratadine with P-glycoprotein. Drug Metab Dispos 29:1080–1083.
  • Wang, W., Sasaki, H., Chien, D-S., Lee, V.H.L. (1991). Lipophilicity influence on conjunctival drug penetration in the pigmented rabbit: a comparison with corneal penetration. Curr Eye Res 10:571–579.
  • Watelet, J.B., Van Cauwenberge, P. (1999). Applied anatomy and physiology of the nose and paranasal sinuses. Allergy 54(Suppl 57):14–25.
  • Watsky, M.A., Jablonski, M.M., Edelhauser, H.F. (1988). Comparison of conjunctival and corneal surface areas in rabbit and human. Curr Eye Res 7:483–486.
  • Weil, A., Caldwell, J., Strolin Benedetti, M., Dostert, P. (1987). Species differences in the metabolic disposition of fenofibrate. In: Paoletti, R., et al. (Ed.), Drugs Affecting Lipid Metabolism. Berlin/Heidelberg: Springer-Verlag.
  • Weliky, I., Howard, J.R., Wichmann, J.K. (1990). Absolute bioavailability (AB) and pharmacokinetics (PK) of azelastine (AZ) [abstract]. Pharmacol Res 22(Suppl 7):S247.
  • Wexler, D.B., Davidson, T.M. (2004). The nasal value: a review of the anatomy, imaging, and physiology. Am J Rhinol 18:143–150.
  • Whomsley, R., Strolin Benedetti, M. (2005). Development of new H1 antihistamines: the importance of pharmacokinetics in the evaluation of safe and therapeutically effective agents. Curr Med Chem 4:451–464.
  • Wilding, I. (2005). Use of human microdosing studies to improve the pharmacokinetic/bioavailability (PK/BA) quality of new drug candidates. In: Luscombe, D., Stonier, P.D. (Eds.), Clincal Research Manual Supplement 19. Euromed Communications. Haslemere, UK.
  • Wilding, I.R., Bell, J.A. (2005). Improved early clinical development through human microdosing studies. Drug Discov Today 10:890–894.
  • Willsie, S.K. (2002). Improved strategies and new treatment options for allergic rhinitis. J Am Osteopath Assoc 102(Suppl 2):7–14.
  • Windmill, K.F., Gaedigk, A., Hall, P.M., Samaratunga, H., Grant, D.M., McManus, M.E. (2000). Localization of N-acetyltransferases NAT1 and NAT2 in human tissues. Toxicol Sci 54:19–29.
  • Winkler, J., Hochhaus, G., Derendorf, H. (2004). How the lung handles drugs. Pharmacokinetics and pharmacodynamics of inhaled corticosteroids. Proc Am Thorac Soc 1:356–363.
  • Xia, C.Q., Milton, M.N., Gan, L.S. (2007). Evaluation of drug- transporter interactions using in vitro and in vivo models. Curr Drug Metab 8:341–363.
  • Xia, C.Q., Yang, J.Y., Balani, S.K. (2008). Drug Transporters in Drug Disposition, Drug Interactions, and Drug Resistance in Drug Metabolism in Drug Design and Development. Hoboken, New Jersey, USA: John Wiley & Sons.
  • Yumibe, N., Huie, K., Chen, K.J., Snow, M., Clement, R.P., Cayen, M.N. (1996). Identification of human liver cytochrome P450 enzymes that metabolize the nonsedating antihistamine loratadine. Formation of descarboethoxyloratadine by CYP3A4 and CYP2D6. Biochem Pharmacol 51:165–172.
  • Zaki, I., Fitzgerald, P., Hardy, J.G., Wilson, C.G. (1989). A comparison of the effect of viscosity on the precorneal residence of solutions in rabbit and man. J Pharm Pharmacol 38:463–466.
  • Zamek-Gliszczynski, M.J., Hoffmaster, K.A., Nezasa, K., Tallman, M.N., Brouwer, K.L. (2006). Integration of hepatic drug transporters and phase II metabolizing enzymes: mechanisms of hepatic excretion of sulfate, glucuronide, and glutathione metabolites. Eur J Pharm Sci 27:447–486.
  • Zazgornik, J., Huang, M.L., Van Peer, A., Woestenborghs, R., Heykants, J., Stephen, A. (1993). Pharmacokinetics of orally administered levocabastine in patients with renal insufficiency. J Clin Pharmacol 33:1214–1218.
  • Zeldin, D.C., Foley, J., Ma, J., Boyle, J.E., Pascual, J.M.S., Moomaw, C.R., et al. (1996). CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance. Mol Pharmacol 50:1111–1117.
  • Zhang, L., Strong, J.M., Qiu, W., Lesko, L.J., Huang, S.M. (2006). Scientific perspectives on drug transporters and their role in drug interactionst. Mol Pharm 3:62–69.
  • Zhang, X., Zhang, Q-Y., Liu, D., Su, T., Weng, Y., Ling, G., et al. (2005). Expression of cytochrome P450 and other biotransformation genes in fetal and adult human nasal mucosa. Drug Metab Dispos 33:1423–1428.
  • Zhou, S.F., Wang, L.L., Di, Y.M., Xue, C.C., Duan, W., Li, C.G., et al. (2008). Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development. Curr Med Chem 15:1981–2039.
  • Zitt, M., Kosoglou, T., Hubbell, J. (2007). Mometasone furoate nasal spray. A review of safety and systemic effects. Drug Saf 30:317–326.
  • Zitt, M.J. (2005). Properties of the ideal corticosteroid therapy. Allergy Asthma Proc 26:173–182.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.