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Xenobiotica
the fate of foreign compounds in biological systems
Volume 36, 2006 - Issue 6
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Research Article

Prediction of in vivo drug clearance from in vitro data. I: Impact of inter-individual variability

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Pages 473-497 | Received 23 Nov 2005, Published online: 22 Sep 2008

References

  • Abelo A, Andersson TB, Antonsson M, Naudot AK, Skanberg I, Weidolf L. Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metabolism and Disposition 2000; 28: 966–972
  • Abernethy DR, Kaminsky LS, Dickinson TH. Selective inhibition of warfarin metabolism by diltiazem in humans. Journal of Pharmacology and Experimental Therapeutics 1991; 257: 411–415
  • Aitchison J, Brown JAC. The lognormal distribution. Cambridge University Press, Cambridge 1966
  • Allonen H, Ziegler G, Klotz U. Midazolam kinetics. Clinical Pharmacology and Therapeutics 1981; 30: 653–661
  • Amchin J, Zarycranski W, Taylor KP, Albano D, Klockowski PM. Effect of venlafaxine on the pharmacokinetics of alprazolam. Psychopharmacology Bulletin 1998; 34: 211–219
  • Andersson T, Andren K, Cederberg C, Lagerstrom PO, Lundborg P, Skanberg I. Pharmacokinetics and bioavailability of omeprazole after single and repeated oral administration in healthy subjects. British Journal of Clinical Pharmacology 1990b; 29: 557–563
  • Andersson T, Cederberg C, Regardh CG, Skanberg I. Pharmacokinetics of various single intravenous and oral doses of omeprazole. European Journal of Clinical Pharmacology 1990a; 39: 195–197
  • Austin RP, Barton P, Cockroft SL, Wenlock MC, Riley RJ. The influence of nonspecific microsomal binding on apparent intrinsic clearance, and its prediction from physicochemical properties. Drug Metabolism and Disposition 2002; 30: 1497–1503
  • Awni WM, Hussein Z, Granneman GR, Patterson KJ, Dube LM, Cavanaugh JH. Pharmacodynamic and stereoselective pharmacokinetic interactions between zileuton and warfarin in humans. Clinical Pharmacokinetics 1995; 29(Suppl. 2)67–76
  • Barbhaiya RH, Shukla UA, Kroboth PD, Greene DS. Coadministration of nefazodone and benzodiazepines: II. A pharmacokinetic interaction study with triazolam. Journal of Clinical Psychopharmacology 1995; 15: 320–326
  • Barnhart JW. The urinary excretion of dextromethorphan and three metabolites in dogs and humans. Toxicology and Applied Pharmacology 1980; 55: 43–48
  • Birkett DJ, Miners JO. Caffeine renal clearance and urine caffeine concentrations during steady state dosing. Implications for monitoring caffeine intake during sports events. British Journal of Clinical Pharmacology 1991; 31: 405–408
  • Black DJ, Kunze KL, Wienkers LC, Gidal BE, Seaton TL, McDonnell ND, Evans JS, Bauwens JE, Trager WF. Warfarin-fluconazole. II. A metabolically based drug interaction: In vivo studies. Drug Metabolism and Disposition 1996; 24: 422–428
  • Brown HS, Kiyomi I, Galetin A, Houston JB. Prediction of in vivo drug–drug interactions from in vitro data: Impact of incorporating parallel pathways of drug elimination and inhibitor absorption rate constant. British Journal of Clinical Pharmacology 2005; 60: 508–518
  • Brynne N, Dalen P, Alvan G, Bertilsson L, Gabrielsson J. Influence of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamic of tolterodine. Clinical Pharmacology and Therapeutics 1998; 63: 529–539
  • Brynne N, Svanstrom C, Aberg-Wistedt A, Hallen B, Bertilsson L. Fluoxetine inhibits the metabolism of tolterodine – pharmacokinetic implications and proposed clinical relevance. British Journal of Clinical Pharmacology 1999; 48: 553–563
  • Capon DA, Bochner F, Kerry N, Mikus G, Danz C, Somogyi AA. The influence of CYP2D6 polymorphism and quinidine on the disposition and antitussive effect of dextromethorphan in humans. Clinical Pharmacology and Therapeutics 1996; 60: 295–307
  • Carlile DJ, Hakooz N, Bayliss MK, Houston JB. Microsomal prediction of in vivo clearance of CYP2C9 substrates in humans. British Journal of Clinical Pharmacology 1999; 47: 625–635
  • Carrillo JA, Christensen M, Ramos SI, Alm C, Dahl ML, Benitez J, Bertilsson L. Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urine. Therapeutic Drug Monitoring 2000; 22: 409–417
  • Chan E, McLachlan A, O'Reilly R, Rowland M. Stereochemical aspects of warfarin drug interactions: Use of a combined pharmacokinetic–pharmacodynamic model. Clinical Pharmacology and Therapeutics 1994; 56: 286–294
  • Cheng YF, Lundberg T, Bondesson U, Lindstrom L, Gabrielsson J. Clinical pharmacokinetics of clozapine in chronic schizophrenic patients. European Journal of Clinical Pharmacology 1988; 34: 445–449
  • Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41
  • Coller JK, Somogyi AA, Bochner F. Comparison of (S)-mephenytoin and proguanil oxidation in vitro: Contribution of several CYP isoforms. British Journal of Clinical Pharmacology 1999; 48: 158–167
  • Dai Y, Iwanaga K, Lin YS, Hebert MF, Davis CL, Huang W, Kharasch ED, Thummel KE. In vitro metabolism of cyclosporine A by human kidney CYP3A5. Biochemical Pharmacology 2004; 68: 1889–1902
  • Delaporte E, Slaughter DE, Egan MA, Gatto GJ, Santos A, Shelley J, Price E, Howells L, Dean DC, Rodrigues AD. The potential for CYP2D6 inhibition screening using a novel scintillation proximity assay-based approach. Journal of Biomolecular Screening 2001; 6: 225–231
  • Derry CL, Kroboth PD, Pittenger AL, Kroboth FJ, Corey SE, Smith RB. Pharmacokinetics and pharmacodynamics of triazolam after two intermittent doses in obese and normal-weight men. Journal of Clinical Psychopharmacology 1995; 15: 197–205
  • Drover DR, Lemmens HJM, Naidu S, Cevallos WH, Martin P, Stanski D. The comparative pharmacokinetics of zaleplon and zolpidem. Clinical Pharmacology and Therapeutics 1999; 65: 168, (PII-185)
  • Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight are known. Archives of Internal Medicine 1916; 17: 863–871
  • Ducharme MP, Warbasse LH, Edwards DJ. Disposition of intravenous and oral cyclosporine after administration with grapefruit juice. Clinical Pharmacology and Therapeutics 1995a; 57: 485–491
  • Eap CB, Schnyder C, Besson J, Savary L, Buclin T. Inhibition of CYP2E1 by chlormethiazole as measured by chlorzoxazone pharmacokinetics in patients with alcoholism and in healthy volunteers. Clinical Pharmacology and Therapeutics 1998; 64: 52–57
  • Eberts FS, Jr, Philopoulos Y, Reineke LM, Vliek RW. Triazolam disposition. Clinical Pharmacology and Therapeutics 1981; 29: 81–93
  • Eiermann B, Engel G, Johansson I, Zanger UM, Bertilsson L. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. British Journal of Clinical Pharmacology 1997; 44: 439–446
  • Emery MG, Fisher JM, Chien JY, Kharasch ED, Dellinger EP, Kowdley KV, Thummel KE. CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease. Hepatology 2003; 38: 428–435
  • Erens B, Primatesta P. Health survey for England. Cardiovascular disease'98. Vol. 1. Findings. Stationery Office, London 1999
  • Fraser AD. Urinary screening for alprazolam, triazolam, and their metabolites with the EMIT d. a. u. benzodiazepine metabolite assay. Journal of Analytical Toxicology 1987; 11: 263–266
  • Fraser AD, Bryan W, Isner AF. Urinary screening for alprazolam and its major metabolites by the Abbott ADx and TDx analyzers with confirmation by GC/MS. Journal of Analytical Toxicology 1991; 15: 25–29
  • Friedman H, Greenblatt DJ, Burstein ES, Harmatz JS, Shader RI. Population study of triazolam pharmacokinetics. British Journal of Clinical Pharmacology 1986; 22: 639–642
  • Frye RF, Mauro K, Adedoyin A, Matzke GR, Branch RA. Nonlinear pharmacokinetics of chlorzoxazone in humans. Clinical Pharmacology and Therapeutics 1995; 57: 217, (PIII-290)
  • Galetin A, Brown C, Hallifax D, Ito K, Houston JB. Utility of recombinant enzyme kinetics in prediction of human clearance: Impact of variability, CYP3A5, and CYP2C19 on CYP3A4 probe substrates. Drug Metabolism and Disposition 2004; 32: 1411–1420
  • Ghosal A, Satoh H, Thomas PE, Bush E, Moore D. Inhibition and kinetics of cytochrome P4503A activity in microsomes from rat, human, and cDNA-expressed human cytochrome P450. Drug Metabolism and Disposition 1996; 24: 940–947
  • Gorski JC, Hall SD, Jones DR, VandenBranden M, Wrighton SA. Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. Biochemical Pharmacology 1994; 47: 1643–1653
  • Greenblatt DJ, Abernethy DR, Locniskar A, Harmatz JS, Limjuco RA, Shader RI. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology 1984; 61: 27–35
  • Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, Shader RI. Reduced clearance of triazolam in old age: Relation to antipyrine oxidizing capacity. British Journal of Clinical Pharmacology 1983a; 15: 303–309
  • Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, Shader RI. Alprazolam kinetics in the elderly. Relation to antipyrine disposition. Archives of General Psychiatry 1983b; 40: 287–290
  • Greenblatt DJ, Harmatz JS, Dorsey C, Shader RI. Comparative single-dose kinetics and dynamics of lorazepam, alprazolam, prazepam, and placebo. Clinical Pharmacology and Therapeutics 1988; 44: 326–334
  • Greenblatt DJ, Harmatz JS, Von Moltke LL, Ehrenberg BL, Harrel L, Corbett K, Counihan M, Graf JA, Darwish M, Mertzanis P, Martin PT, Cevallos WH, Shader RI. Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo. Clinical Pharmacology and Therapeutics 1998c; 64: 553–561
  • Greenblatt DJ, Harmatz JS, Von Moltke LL, Wright CE, Durol AL, Harrel-Joseph LM, Shader RI. Comparative kinetics and response to the benzodiazepine agonists triazolam and zolpidem: Evaluation of sex-dependent differences. Journal of Pharmacology and Experimental Therapeutics 2000b; 293: 435–443
  • Greenblatt DJ, Von Moltke LL, Harmatz JS, Counihan M, Graf JA, Durol AL, Mertzanis P, Duan SX, Wright CE, Shader RI. Inhibition of triazolam clearance by macrolide antimicrobial agents: In vitro correlates and dynamic consequences. Clinical Pharmacology and Therapeutics 1998b; 64: 278–285
  • Greenblatt DJ, Von Moltke LL, Harmatz JS, Durol AL, Daily JP, Graf JA, Mertzanis P, Hoffman JL, Shader RI. Alprazolam-ritonavir interaction: Implications for product labeling. Clinical Pharmacology and Therapeutics 2000a; 67: 335–341
  • Greenblatt DJ, Von Moltke LL, Harmatz JS, Durol AL, Daily JP, Graf JA, Mertzanis P, Hoffman JL, Shader RI. Differential impairment of triazolam and zolpidem clearance by ritonavir. Journal of Acquired Immune Deficiency Syndromes 2000c; 24: 129–136
  • Greenblatt DJ, Von Moltke LL, Harmatz JS, Mertzanis P, Graf JA, Durol AL, Counihan M, Roth-Schechter B, Shader RI. Kinetic and dynamic interaction study of zolpidem with ketoconazole, itraconazole, and fluconazole. Clinical Pharmacology and Therapeutics 1998d; 64: 661–671
  • Greenblatt DJ, Wright CE, Von Moltke LL, Harmatz JS, Ehrenberg BL, Harrel LM, Corbett K, Counihan M, Tobias S, Shader RI. Ketoconazole inhibition of triazolam and alprazolam clearance: Differential kinetic and dynamic consequences. Clinical Pharmacology and Therapeutics 1998a; 64: 237–247
  • Grevel J, Nuesch E, Abisch E, Kutz K. Pharmacokinetics of oral cyclosporin A (Sandimmun) in healthy subjects. European Journal of Clinical Pharmacology 1986; 31: 211–216
  • Grind M, Murphy M, Warrington S, Aberg J. Method for studying drug–warfarin interactions. Clinical Pharmacology and Therapeutics 1993; 54: 381–387
  • Guyton AC, Hall JE. Cardiac output, venous return, and their regulation. Textbook of Medical Physiology, AC Guyton, JE Hall. W. B. Saunders, Philadelphia 1996
  • Ha HR, Chen J, Krahenbuhl S, Follath F. Biotransformation of caffeine by cDNA-expressed human cytochromes P-450. European Journal of Clinical Pharmacology 1996; 49: 309–315
  • Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. British Journal of Clinical Pharmacology 2000; 49: 59–63
  • Hamaoka N, Oda Y, Hase I, Mizutani K, Nakamoto T, Ishizaki T, Asada A. Propofol decreases the clearance of midazolam by inhibiting CYP3A4: An in vivo and in vitro study. Clinical Pharmacology and Therapeutics 1999; 66: 110–117
  • Hanna IH, Reed JR, Guengerich FP, Hollenberg PF. Expression of human cytochrome P450 2B6 in Escherichia coli: Characterization of catalytic activity and expression levels in human liver. Archives of Biochemistry and Biophysiology 2000; 376: 206–216
  • Heimark LD, Wienkers L, Kunze K, Gibaldi M, Eddy AC, Trager WF, O'Reilly RA, Goulart DA. The mechanism of the interaction between amiodarone and warfarin in humans. Clinical Pharmacology and Therapeutics 1992; 51: 398–407
  • Heinemann A, Wischhusen F, Puschel K, Rogiers X. Standard liver volume in the Caucasian population. Liver Transplantation and Surgery 1999; 5: 366–368
  • Heizmann P, Eckert M, Ziegler WH. Pharmacokinetics and bioavailability of midazolam in man. British Journal of Clinical Pharmacology 1983; 16(Suppl. 1)43S–49S
  • Heyn H, White RB, Stevens JC. Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin. Drug Metabolism and Disposition 1996; 24: 948–954
  • Hirota N, Ito K, Iwatsubo T, Green CE, Tyson CA, Shimada N, Suzuki H, Sugiyama Y. In vitro/in vivo scaling of alprazolam metabolism by CYP3A4 and CYP3A5 in humans. Biopharmaceutics and Drug Disposition 2001; 22: 53–71
  • Houston JB, Carlile DJ. Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices. Drug Metabolism Reviews 1997; 29: 891–922
  • Houston JB, Kenworthy KE. In vitro–in vivo scaling of CYP kinetic data not consistent with the classical Michaelis–Menten model. Drug Metabolism and Disposition 2000; 28: 246–254
  • Hyland R, Roe EG, Jones BC, Smith DA. Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. British Journal of Clinical Pharmacology 2001; 51: 239–248
  • Ibrahim A, Karim A, Feldman J, Kharasch E. The influence of parecoxib, a parenteral cyclooxygenase-2 specific inhibitor, on the pharmacokinetics and clinical effects of midazolam. Anesthesia and Analgesia 2002; 95: 667–673
  • Ito K, Hallifax D, Obach RS, Houston JB. Impact of parallel pathways of drug elimination and multiple cytochrome P450 involvement on drug–drug interactions: CYP2D6 paradigm. Drug Metabolism and Disposition 2005; 33: 837–844
  • Iwata H, Fujita K, Kushida H, Suzuki A, Konno Y, Nakamura K, Fujino A, Kamataki T. High catalytic activity of human cytochrome P450 co-expressed with human NADPH-cytochrome P450 reductase in Escherichia coli. Biochemical Pharmacology 1998; 55: 1315–1325
  • Iwatsubo T, Hirota N, Ooie T, Suzuki H, Sugiyama Y. Prediction of in vivo drug disposition from in vitro data based on physiological pharmacokinetics. Biopharmaceutics and Drug Disposition 1996; 17: 273–310
  • Jacqz E, Hall SD, Branch RA, Wilkinson GR. Polymorphic metabolism of mephenytoin in man: Pharmacokinetic interaction with a co-regulated substrate, mephobarbital. Clinical Pharmacology and Therapeutics 1986; 39: 646–653
  • Johnson TN. Modelling approaches to dose estimation in children. British Journal of Clinical Pharmacology 2005; 59: 663–669
  • Johnson TN, Rostami-Hodjegan A, Tucker GT. Prediction of 11 drugs and associated variability in neonates, infants and children. Clinical Pharmacokinetics 2005, (in press)
  • Kanamitsu S, Ito K, Green CE, Tyson CA, Shimada N, Sugiyama Y. Prediction of in vivo interaction between triazolam and erythromycin based on in vitro studies using human liver microsomes and recombinant human CYP3A4. Pharmaceutical Research 2000; 17: 419–426
  • Kaplan GB, Greenblatt DJ, Ehrenberg BL, Goddard JE, Harmatz JS, Shader RI. Single-dose pharmacokinetics and pharmacodynamics of alprazolam in elderly and young subjects. Journal of Clinical Pharmacology 1998; 38: 14–21
  • Karam WG, Goldstein JA, Lasker JM, Ghanayem BI. Human CYP2C19 is a major omeprazole 5-hydroxylase, as demonstrated with recombinant cytochrome P450 enzymes. Drug Metabolism and Disposition 1996; 24: 1081–1087
  • Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T. Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: Prediction of in vivo drug–drug interactions. European Journal of Clinical Pharmacology 2000; 55: 843–852
  • Kim RB, Chiba K, Ishizaki T, Wilkinson GR. Chlorzoxazone (CZX) 6-hydroxylation in Japanese and Caucasians. Clinical Pharmacology and Therapeutics 1995; 57: 217, (PIII-292)
  • Kim RB, O'Shea D. Interindividual variability of chlorzoxazone 6-hydroxylation in men and women and its relationship to CYP2E1 genetic polymorphisms. Clinical Pharmacology and Therapeutics 1995; 57: 645–655
  • Kinirons MT, Lang CC, He HB, Ghebreselasie K, Shay S, Robin DW, Wood AJ. Triazolam pharmacokinetics and pharmacodynamics in Caucasians and Southern Asians: Ethnicity and CYP3A activity. British Journal of Clinical Pharmacology 1996; 41: 69–72
  • Kirchheiner J, Bauer S, Meineke I, Rohde W, Prang V, Meisel C, Roots I, Brockmoller J. Impact of CYP2C9 and CYP2C19 polymorphisms on tolbutamide kinetics and the insulin and glucose response in healthy volunteers. Pharmacogenetics 2002; 12: 101–109
  • Kirkwood C, Moore A, Hayes P, DeVane CL, Pelonero A. Influence of menstrual cycle and gender on alprazolam pharmacokinetics. Clinical Pharmacology and Therapeutics 1991; 50: 404–409
  • Klotz U, Ziegler G. Physiologic and temporal variation in hepatic elimination of midazolam. Clinical Pharmacology and Therapeutics 1982; 32: 107–112
  • Knodell RG, Hall SD, Wilkinson GR, Guengerich FP. Hepatic metabolism of tolbutamide: Characterization of the form of cytochrome P-450 involved in methyl hydroxylation and relationship to in vivo disposition. Journal of Pharmacology and Experimental Therapeutics 1987; 241: 1112–1119
  • Ko JW, Desta Z, Flockhart DA. Human N-demethylation of (S)-mephenytoin by cytochrome P450s 2C9 and 2B6. Drug Metabolism and Disposition 1998; 26: 775–778
  • Kroboth PD, McAuley JW, Kroboth FJ, Bertz RJ, Smith RB. Triazolam pharmacokinetics after intravenous, oral, and sublingual administration. Journal of Clinical Psychopharmacology 1995; 15: 259–262
  • Kronbach T, Mathys D, Umeno M, Gonzalez FJ, Meyer UA. Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Molecular Pharmacology 1989; 36: 89–96
  • Kupfer A, Desmond PV, Schenker S, Branch RA. Stereoselective metabolism and disposition of the enantiomers of mephenytoin during chronic oral administration of the racemic drug in man. Journal of Pharmacology and Experimental Therapeutics 1982; 221: 590–597
  • Lasker JM, Wester MR, Aramsombatdee E, Raucy JL. Characterization of CYP2C19 and CYP2C9 from human liver: Respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations. Archives of Biochemistry and Biophysiology 1998; 353: 16–28
  • Lee CR, Pieper JA, Hinderliter AL, Blaisdell JA, Goldstein JA. Evaluation of cytochrome P4502C9 metabolic activity with tolbutamide in CYP2C91 heterozygotes. Clinical Pharmacology and Therapeutics 2002; 72: 562–571
  • Legg B, Rowland M. Cyclosporin: Measurement of fraction unbound in plasma. Journal of Pharmacy and Pharmacology 1987; 39: 599–603
  • Lelo A, Birkett DJ, Robson RA, Miners JO. Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man. British Journal of Clinical Pharmacology 1986; 22: 177–182
  • Lewis DF. Structural characteristics of human P450s involved in drug metabolism: QSARs and lipophilicity profiles. Toxicology 2000; 144: 197–203
  • Lin KM, Lau JK, Smith R, Phillips P, Antal E, Poland RE. Comparison of alprazolam plasma levels in normal Asian and Caucasian male volunteers. Psychopharmacology (Berlin) 1988; 96: 365–369
  • Lin Y, Lu P, Tang C, Mei Q, Sandig G, Rodrigues AD, Rushmore TH, Shou M. Substrate inhibition kinetics for cytochrome P450-catalyzed reactions. Drug Metabolism and Disposition 2001; 29: 368–374
  • Linnet K, Olesen OV. Metabolism of clozapine by cDNA-expressed human cytochrome P450 enzymes. Drug Metabolism and Disposition 1997; 25: 1379–1382
  • Madsen H, Enggaard TP, Hansen LL, Klitgaard NA, Brosen K. Fluvoxamine inhibits the CYP2C9 catalyzed biotransformation of tolbutamide. Clinical Pharmacology and Therapeutics 2001; 69: 41–47
  • Mallikaarjun S, Bramer SL. Effect of cilostazol on the pharmacokinetics and pharmacodynamics of warfarin. Clinical Pharmacokinetics 1999; 37(Suppl. 2)79–86
  • Mankowski DC, Lawton MP, Ekins S. Characterization of transgenic mouse strains using six human hepatic cytochrome P450 probe substrates. Xenobiotica 2000; 30: 745–754
  • Masica AL, Mayo G, Wilkinson GR. In vivo comparisons of constitutive cytochrome P450 3A activity assessed by alprazolam, triazolam, and midazolam. Clinical Pharmacology and Therapeutics 2004; 76: 341–349
  • Masimirembwa CM, Otter C, Berg M, Jonsson M, Leidvik B, Jonsson E, Johansson T, Backman A, Edlund A, Andersson TB. Heterologous expression and kinetic characterization of human cytochromes P-450: Validation of a pharmaceutical tool for drug metabolism research. Drug Metabolism and Disposition 1999; 27: 1117–1122
  • McLure JA, Miners JO, Birkett DJ. Nonspecific binding of drugs to human liver microsomes. British Journal of Clinical Pharmacology 2000; 49: 453–461
  • Min DI, Lee M, Ku YM, Flanigan M. Gender-dependent racial difference in disposition of cyclo-sporine among healthy African American and white volunteers. Clinical Pharmacology and Therapeutics 2000; 68: 478–486
  • Miners JO, Wing LM, Lillywhite KJ, Smith KJ. Failure of ‘therapeutic’ doses of beta-adrenoceptor antagonists to alter the disposition of tolbutamide and lignocaine. British Journal of Clinical Pharmacology 1984; 18: 853–860
  • Moghadamnia AA, Rostami-Hodjegan A, Abdul-Manap R, Wright CE, Morice AH, Tucker GT. Physiologically based modelling of inhibition of metabolism and assessment of the relative potency of drug and metabolite: Dextromethorphan vs. dextrorphan using quinidine inhibition. British Journal of Clinical Pharmacology 2003; 56: 57–67
  • Moschitto LJ, Greenblatt DJ. Concentration-independent plasma protein binding of benzodiazepines. Journal of Pharmacy and Pharmacology 1983; 35: 179–180
  • Muirhead GJ, Allen MJ, James GC, Pearson J, Rance DJ, Houston AC, Dewland PM. Pharmacokinetics of sildenafil (VIAGRA), a selective cGMP PDE5 inhibitor, after single oral doses in fasted and fed healthy volunteers. British Journal of Clinical Pharmacology 1996; 42: 268P
  • Muirhead GJ, Rance DJ, Walker DK, Wastall P. Comparative human pharmacokinetics and metabolism of single-dose oral and intravenous sildenafil. British Journal of Clinical Pharmacology 2002a; 53(Suppl. 1)13S–20S
  • Muirhead GJ, Wilner K, Colburn W, Haug-Pihale G, Rouviex B. The effects of age and renal and hepatic impairment on the pharmacokinetics of sildenafil. British Journal of Clinical Pharmacology 2002b; 53(Suppl. 1)21S–30S
  • Nestorov I, Gueorguieva I, Jones HM, Houston B, Rowland M. Incorporating measures of variability and uncertainty into the prediction of in vivo hepatic clearance from in vitro data. Drug Metabolism and Disposition 2002; 30: 276–282
  • Novartis Pharmaceuticals Corporation. Sandimmune (cyclosporine) capsules. Prescribing information. Novartis Pharmaceuticals Corporation. 2004
  • O'Shea D, Davis SN, Kim RB, Wilkinson GR. Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: A putative probe of CYP2E1 activity. Clinical Pharmacology and Therapeutics 1994; 56: 359–367
  • Obach RS. Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metabolism and Disposition 1999; 27: 1350–1359
  • Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F, Rance DJ, Wastall P. The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. Journal of Pharmacology and Experimental Therapeutics 1997; 283: 46–58
  • Obach RS, Walsky RL, Venkatakrishnan K, Gaman EA, Houston JB, Tremaine LM. The utility of in vitro cytochrome p450 inhibition data in the prediction of drug–drug interactions. Journal of Pharmacology and Experimental Therapeutics 2005; 316: 336–348
  • Ochs HR, Greenblatt DJ, Labedzki L, Smith RB. Alprazolam kinetics in patients with renal insufficiency. Journal of Clinical Psychopharmacology 1986; 6: 292–294
  • Oda Y, Mizutani K, Hase I, Nakamoto T, Hamaoka N, Asada A. Fentanyl inhibits metabolism of midazolam: Competitive inhibition of CYP3A4 in vitro. British Journal of Anaesthesia 1999; 82: 900–903
  • Olubodun JO, Ochs HR, Von Moltke LL, Roubenoff R, Hesse LM, Harmatz JS, Shader RI, Greenblatt DJ. Pharmacokinetic properties of zolpidem in elderly and young adults: Possible modulation by testosterone in men. British Journal of Clinical Pharmacology 2003; 56: 297–304
  • Pahlman I, Gozzi P. Serum protein binding of tolterodine and its major metabolites in humans and several animal species. Biopharmaceutics and Drug Disposition 1999; 20: 91–99
  • Paine MF, Khalighi M, Fisher JM, Shen DD, Kunze KL, Marsh CL, Perkins JD, Thummel KE. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. Journal of Pharmacology and Experimental Therapeutics 1997; 283: 1552–1562
  • Palamanda J, Feng WW, Lin CC, Nomeir AA. Stimulation of tolbutamide hydroxylation by acetone and acetonitrile in human liver microsomes and in a cytochrome P-450 2C9-reconstituted system. Drug Metabolism and Disposition 2000; 28: 38–43
  • Patat A, Trocherie S, Thebault JJ, Rosenzweig P, Dubruc C, Bianchetti G, Court LA, Morselli PL. EEG profile of intravenous zolpidem in healthy volunteers. Psychopharmacology (Berlin) 1994; 114: 138–146
  • Patki KC, Von Moltke LL, Greenblatt DJ. In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: Role of cyp3a4 and cyp3a5. Drug Metabolism and Disposition 2003; 31: 938–944
  • Peart GF, Boutagy J, Shenfield GM. Lack of relationship between tolbutamide metabolism and debrisoquine oxidation phenotype. European Journal of Clinical Pharmacology 1987; 33: 397–402
  • Pharmacia Corporation. Detrol (tolterodine tartrate) tablets. Prescribing information. Pharmacia Corporation. 2003
  • Pichard L, Domergue J, Fourtanier G, Koch P, Schran HF, Maurel P. Metabolism of the new immunosuppressor cyclosporin G by human liver cytochromes P450. Biochemical Pharmacology 1996; 51: 591–598
  • Poloyac SM, Tosheva RT, Gardner BM, Shedlofsky SI, Blouin RA. The effect of endotoxin administration on the pharmacokinetics of chlorzoxazone in humans. Clinical Pharmacology and Therapeutics 1999; 66: 554–562
  • Postlind H, Danielson A, Lindgren A, Andersson SH. Tolterodine, a new muscarinic receptor antagonist, is metabolized by cytochromes P450 2D6 and 3A in human liver microsomes. Drug Metabolism and Disposition 1998; 26: 289–293
  • Poulin P, Theil FP. Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution. Journal of Pharmaceutical Sciences 2002; 91: 129–156
  • Priskorn M, Sidhu JS, Larsen F, Davis JD, Khan AZ, Rolan PE. Investigation of multiple dose citalopram on the pharmacokinetics and pharmacodynamics of racemic warfarin. British Journal of Clinical Pharmacology 1997; 44: 199–202
  • Proctor NJ, Tucker GT, Rostami-Hodjegan A. Predicting drug clearance from recombinantly expressed CYPs: Intersystem extrapolation factors. Xenobiotica 2004; 34: 151–178
  • Rane A, Wilkinson GR, Shand DG. Prediction of hepatic extraction ratio from in vitro measurement of intrinsic clearance. Journal of Pharmacology and Experimental Therapeutics 1977; 200: 420–424
  • Regardh CG, Andersson T, Lagerstrom PO, Lundborg P, Skanberg I. The pharmacokinetics of omeprazole in humans – a study of single intravenous and oral doses. Therapeutic Drug Monitoring 1990; 12: 163–172
  • Regardh CG, Gabrielsson M, Hoffman KJ, Lofberg I, Skanberg I. Pharmacokinetics and metabolism of omeprazole in animals and man – an overview. Scandinavian Journal of Gastroenterology Suppl. 1985; 108: 79–94
  • Robertson P, Jr, Hellriegel ET, Arora S, Nelson M. Effect of modafinil at steady state on the single-dose pharmacokinetic profile of warfarin in healthy volunteers. Journal of Clinical Pharmacology 2002; 42: 205–214
  • Rostami-Hodjegan A, Peacey SR, George E, Heller SR, Tucker GT. Population-based modeling to demonstrate extrapancreatic effects of tolbutamide. American Journal of Physiology 1998; 274: E758–E771
  • Rostami-Hodjegan A, Tucker GT. The effects of portal shunts on intestinal cytochrome P450 3A activity. Hepatology 2002; 35: 1549–1550, author reply 1550–1541
  • Rostami-Hodjegan A, Tucker GT. ‘In silico’ simulations to assess the ‘in vivo’ consequences of ‘in vitro’ metabolic drug–drug interactions. Drug Discovery Today: Technologies 2004; 1: 441–448
  • Rowland M, Tozer TN. Clinical pharmacokinetics concepts and applications3rd. Lippincott: Williams & Wilkins, Philadelphia, PA 1995; 230–247
  • Rowland-Yeo K, Rostami-Hodjegan A, Tucker GT. Abundance of cytochromes P450 in human liver: A meta-analysis. British Journal of Clinical Pharmacology 2004; 57: 687
  • Salva P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clinical Pharmacokinetics 1995; 29: 142–153
  • Scavone JM, Greenblatt DJ, Locniskar A, Shader RI. Alprazolam pharmacokinetics in women on low-dose oral contraceptives. Journal of Clinical Pharmacology 1988; 28: 454–457
  • Schaber G, Stevens I, Gaertner HJ, Dietz K, Breyer-Pfaff U. Pharmacokinetics of clozapine and its metabolites in psychiatric patients: Plasma protein binding and renal clearance. British Journal of Clinical Pharmacology 1998; 46: 453–459
  • Schadel M, Wu D, Otton SV, Kalow W, Sellers EM. Pharmacokinetics of dextromethorphan and metabolites in humans: Influence of the CYP2D6 phenotype and quinidine inhibition. Journal of Clinical Psychopharmacology 1995; 15: 263–269
  • Schrag ML, Wienkers LC. Triazolam substrate inhibition: Evidence of competition for heme-bound reactive oxygen within the CYP3A4 active site. Drug Metabolism and Disposition 2001; 29: 70–75
  • Shimada T, Tsumura F, Yamazaki H. Prediction of human liver microsomal oxidations of 7-ethoxycoumarin and chlorzoxazone with kinetic parameters of recombinant cytochrome P-450 enzymes. Drug Metabolism and Disposition 1999; 27: 1274–1280
  • Soto J, Alsar MJ. A pilot study of the effect of antipyrine on caffeine kinetics in six healthy volunteer subjects. Journal of Clinical Pharmacy and Therapeutics 1997; 22: 191–195
  • Stein CM, Sadeque AJ, Murray JJ, Wandel C, Kim RB, Wood AJ. Cyclosporine pharmacokinetics and pharmacodynamics in African American and white subjects. Clinical Pharmacology and Therapeutics 2001; 69: 317–323
  • Sullivan-Klose TH, Ghanayem BI, Bell DA, Zhang ZY, Kaminsky LS, Shenfield GM, Miners JO, Birkett DJ, Goldstein JA. The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 1996; 6: 341–349
  • Takahashi H, Kashima T, Kimura S, Murata N, Takaba T, Iwade K, Abe T, Tainaka H, Yasumori T, Echizen H. Pharmacokinetic interaction between warfarin and a uricosuric agent, bucolome: Application of in vitro approaches to predicting in vivo reduction of (S)-warfarin clearance. Drug Metabolism and Disposition 1999; 27: 1179–1186
  • Takahashi H, Kashima T, Nomoto S, Iwade K, Tainaka H, Shimizu T, Nomizo Y, Muramoto N, Kimura S, Echizen H. Comparisons between in-vitro and in-vivo metabolism of (S)-warfarin: Catalytic activities of cDNA-expressed CYP2C9, its Leu359 variant and their mixture versus unbound clearance in patients with the corresponding CYP2C9 genotypes. Pharmacogenetics 1998; 8: 365–373
  • Takanashi K, Tainaka H, Kobayashi K, Yasumori T, Hosakawa M, Chiba K. CYP2C9 Ile359 and Leu359 variants: Enzyme kinetic study with seven substrates. Pharmacogenetics 2000; 10: 95–104
  • Tan KK, Trull AK, Shawket S. Co-administration of ciprofloxacin and cyclosporin: Lack of evidence for a pharmacokinetic interaction. British Journal of Clinical Pharmacology 1989; 28: 185–187
  • Tang H, Mayersohn M. A novel model for prediction of human drug clearance by allometric scaling. Drug Metabolism and Disposition 2005a; 33: 1297–1303
  • Tang H, Mayersohn M. Accuracy of allometrically predicted pharmacokinetic parameters in humans: Role of species selection. Drug Metabolism and Disposition 2005b; 33: 1288–1293
  • Tang W, Wang RW, Lu AYH. Utility of recombinant cytochrome P450 enzymes: A drug metabolism perspective. Current Drug Metabolism 2005; 6: 503–517
  • Tantcheva-Poor I, Zaigler M, Rietbrock S, Fuhr U. Estimation of cytochrome P-450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test. Pharmacogenetics 1999; 9: 131–144
  • Tenneze L, Verstuyft C, Becquemont L, Poirier JM, Wilkinson GR, Funck-Brentano C. Assessment of CYP2D6 and CYP2C19 activity in vivo in humans: A cocktail study with dextromethorphan and chloroguanide alone and in combination. Clinical Pharmacology and Therapeutics 1999; 66: 582–588
  • Thummel KE, O'Shea D, Paine MF, Shen DD, Kunze KL, Perkins JD, Wilkinson GR. Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clinical Pharmacology and Therapeutics 1996; 59: 491–502
  • Tooley A, Rostami-Hodjegan A, Lennard MS, Tucker GT. Acute inhibition of methadone metabolism by ritonavir: Projection of interindividual variability from in vitro data. British Journal of Clinical Pharmacology 1999; 48: 883P–884P
  • Tremaine LM, Wilner KD, Preskorn SH. A study of the potential effect of sertraline on the pharmacokinetics and protein binding of tolbutamide. Clinical Pharmacokinetics 1997; 32(Suppl. 1)31–36
  • Tsunoda SM, Harris RZ, Christians U, Velez RL, Freeman RB, Benet LZ, Warshaw A. Red wine decreases cyclosporine bioavailability. Clinical Pharmacology and Therapeutics 2001; 70: 462–467
  • Tucker GT. The rational selection of drug interaction studies: Implications of recent advances in drug metabolism. International Journal of Clinical Pharmacology and Therapeutics 1992; 30: 550–553
  • Valetin J. Basic anatomical and physiological data for use in radiological protection: Reference values. A report of age- and gender-related differences in the anatomical and physiological characteristics of reference individuals. Annals of the ICRP, Publication 2002; 89 32: 5–265
  • Van Hecken A, Verbesselt R, Depre M, Tjandramaga TB, Angehrn J, Cawello W, De Schepper PJ. Moexipril does not alter the pharmacokinetics or pharmacodynamics of warfarin. European Journal of Clinical Pharmacology 1993; 45: 291–293
  • Von Moltke LL, Greenblatt DJ, Granda BW, Duan SX, Grassi JM, Venkatakrishnan K, Harmatz JS, Shader RI. Zolpidem metabolism in vitro: Responsible cytochromes, chemical inhibitors, and in vivo correlations. British Journal of Clinical Pharmacology 1999; 48: 89–97
  • Von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Venkatakrishnan K, Schmider J, Harmatz JS, Shader RI. Multiple human cytochromes contribute to biotransformation of dextromethorphan in vitro: Role of CYP2C9, CYP2C19, CYP2D6, and CYP3A. Journal of Pharmacy and Pharmacology 1998; 50: 997–1004
  • Von Moltke LL, Greenblatt DJ, Harmatz JS, Duan SX, Harrel LM, Cotreau-Bibbo MM, Pritchard GA, Wright CE, Shader RI. Triazolam biotransformation by human liver microsomes in vitro: Effects of metabolic inhibitors and clinical confirmation of a predicted interaction with ketoconazole. Journal of Pharmacology and Experimental Therapeutics 1996; 276: 370–379
  • Wandel C, Witte JS, Hall JM, Stein CM, Wood AJ, Wilkinson GR. CYP3A activity in African American and European American men: Population differences and functional effect of the CYP3A4* 1B5′-promoter region polymorphism. Clinical Pharmacology and Therapeutics 2000; 68: 82–91
  • Wang RW, Newton DJ, Liu N, Atkins WM, Lu AY. Human cytochrome P-450 3A4: In vitro drug–drug interaction patterns are substrate-dependent. Drug Metabolism and Disposition 2000; 28: 360–366
  • Wang Z, Hall SD, Maya JF, Li L, Asghar A, Gorski JC. Diabetes mellitus increases the in vivo activity of cytochrome P450 2E1 in humans. British Journal of Clinical Pharmacology 2003; 55: 77–85
  • Ward KW, Nagilla R, Jolivette J. Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human. Xenobiotica 2005; 35: 191–210
  • Warrington JS, Shader RI, Von Moltke LL, Greenblatt DJ. In vitro biotransformation of sildenafil (Viagra): Identification of human cytochromes and potential drug interactions. Drug Metabolism and Disposition 2000; 28: 392–397
  • Wedlund PJ, Aslanian WS, Jacqz E, McAllister CB, Branch RA, Wilkinson GR. Phenotypic differences in mephenytoin pharmacokinetics in normal subjects. Journal of Pharmacology and Experimental Therapeutics 1985; 234: 662–669
  • Wietholtz H, Zysset T, Marschall HU, Generet K, Matern S. The influence of rifampin treatment on caffeine clearance in healthy man. Journal of Hepatology 1995; 22: 78–81
  • Wilkinson GR, Shand DG. Commentary: A physiological approach to hepatic drug clearance. Clinical Pharmacology and Therapeutics 1975; 18: 377–390
  • Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA. Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metabolism and Disposition 2002; 30: 883–891
  • Wilner KD, Gardner MJ. Tenidap sodium does not alter the clearance or plasma protein binding of tolbutamide in healthy male volunteers. British Journal of Clinical Pharmacology 1995; 39(Suppl. 1)39S–42S
  • Wilson ZE, Rostami-Hodjegan A, Burn JL, Tooley A, Boyle J, Ellis SW, Tucker GT. Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver. British Journal of Clinical Pharmacology 2003; 56: 433–440
  • Witherow LE, Houston JB. Sigmoidal kinetics of CYP3A substrates: An approach for scaling dextromethorphan metabolism in hepatic microsomes and isolated hepatocytes to predict in vivo clearance in rat. Journal of Pharmacology and Experimental Therapeutics 1999; 290: 58–65
  • Wong SL, Locke C, Staser J, Granneman GR. Lack of multiple dosing effect of sertindole on the pharmacokinetics of alprazolam in healthy volunteers. Psychopharmacology (Berlin) 1998; 135: 236–241
  • Yamazaki H, Inoue K, Chiba K, Ozawa N, Kawai T, Suzuki Y, Goldstein JA, Guengerich FP, Shimada T. Comparative studies on the catalytic roles of cytochrome P450 2C9 and its Cys- and Leu-variants in the oxidation of warfarin, flurbiprofen, and diclofenac by human liver microsomes. Biochemical Pharmacology 1998; 56: 243–251
  • Yamazaki H, Inoue K, Shaw PM, Checovich WJ, Guengerich FP, Shimada T. Different contributions of cytochrome P450 2C19 and 3A4 in the oxidation of omeprazole by human liver microsomes: Effects of contents of these two forms in individual human samples. Journal of Pharmacology and Experimental Therapeutics 1997; 283: 434–442
  • Yang J, Tucker GT, Rostami-Hodjegan A. Cytochrome P450 3A expression and activity in the human small intestine. Clinical Pharmacology and Therapeutics 2004; 76: 931
  • Yang JS, Rostami-Hodjegan A, Tucker GT. Prediction of ketoconazole interaction with midazolam, alprazolam and triazolam: Incorporating population variability. British Journal of Clinical Pharmacology 2001; 52: 472P
  • Yu A, Dong H, Lang D, Haining RL. Characterization of dextromethorphan O- and N-demethylation catalyzed by highly purified recombinant human CYP2D6. Drug Metabolism and Disposition 2001; 29: 1362–1365
  • Yu A, Haining RL. Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro: Can dextromethorphan be used as a dual probe for both CYP2D6 and CYP3A activities?. Drug Metabolism and Disposition 2001; 29: 1514–1520

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