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Review Article

Sources of interindividual variability in IVIVE of clearance: an investigation into the prediction of benzodiazepine clearance using a mechanistic population-based pharmacokinetic model

, , , &
Pages 623-638 | Received 01 Dec 2010, Accepted 31 Jan 2011, Published online: 24 Mar 2011

References

  • Abernethy DR, Greenblatt DJ, Divoll M, Smith RB, Shader RI. (1984). The influence of obesity on the pharmacokinetics of oral alprazolam and triazolam. Clin Pharmacokinet 9:177–183.
  • Allonen H, Ziegler G, Klotz U. (1981). Midazolam kinetics. Clin Pharmacol Ther 30:653–661.
  • Backman JT, Kivistö KT, Olkkola KT, Neuvonen PJ. (1998). The area under the plasma concentration-time curve for oral midazolam is 400-fold larger during treatment with itraconazole than with rifampicin. Eur J Clin Pharmacol 54:53–58.
  • Backman JT, Olkkola KT, Neuvonen PJ. (1995). Azithromycin does not increase plasma concentrations of oral midazolam. Int J Clin Pharmacol Ther 33:356–359.
  • Backman JT, Wang JS, Wen X, Kivistö KT, Neuvonen PJ. (1999). Mibefradil but not isradipine substantially elevates the plasma concentrations of the CYP3A4 substrate triazolam. Clin Pharmacol Ther 66:401–407.
  • Barbhaiya RH, Shukla UA, Kroboth PD, Greene DS. (1995). Coadministration of nefazodone and benzodiazepines: II. A pharmacokinetic interaction study with triazolam. J Clin Psychopharmacol 15:320–326.
  • Barter ZE, Bayliss MK, Beaune PH, Boobis AR, Carlile DJ, Edwards RJ, Houston JB, Lake BG, Lipscomb JC, Pelkonen OR, Tucker GT, Rostami-Hodjegan A. (2007). Scaling factors for the extrapolation of in vivo metabolic drug clearance from in vitro data: reaching a consensus on values of human microsomal protein and hepatocellularity per gram of liver. Curr Drug Metab 8:33–45.
  • Barter ZE, Chowdry JE, Harlow JR, Snawder JE, Lipscomb JC, Rostami-Hodjegan A. (2008). Covariation of human microsomal protein per gram of liver with age: absence of influence of operator and sample storage may justify interlaboratory data pooling. Drug Metab Dispos 36:2405–2409.
  • Barter ZE, Perrett HF, Yeo KR, Allorge D, Lennard MS, Rostami-Hodjegan A. (2010). Determination of a quantitative relationship between hepatic CYP3A5*1/*3 and CYP3A4 expression for use in the prediction of metabolic clearance in virtual populations. Biopharm Drug Dispos 31:516–532.
  • Calvo R, Suárez E, Rodríguez-Sasiain JM, Martínez I. (1992). The influence of renal failure on the kinetics of intravenous midazolam: an “in vitro” and “in vivo” study. Res Commun Chem Pathol Pharmacol 78:311–320.
  • Carr B, Norcross R, Fang Y, Lu P, Rodrigues AD, Shou M, Rushmore T, Booth-Genthe C. (2006). Characterization of the rhesus monkey CYP3A64 enzyme: species comparisons of CYP3A substrate specificity and kinetics using baculovirus-expressed recombinant enzymes. Drug Metab Dispos 34:1703–1712.
  • Chen Y, Liu L, Nguyen K, Fretland AJ. (2010). Utility of inter-system extrapolation factors (ISEFs) in early reaction phenotyping and the quantitative extrapolation of human liver microsomal intrinsic clearance using recombinant cytochrome P450s. Drug Metab Dispos 39:373–382.
  • Ciraulo DA, Barnhill JG, Greenblatt DJ, Shader RI, Ciraulo AM, Tarmey MF, Molloy MA, Foti ME. (1988). Abuse liability and clinical pharmacokinetics of alprazolam in alcoholic men. J Clin Psychiatry 49:333–337.
  • Crewe HK, Barter ZE, Rowland Yeo K, Rostami-Hodjegan A. (2010). Variation in the catalytic activity per unit enzyme of recombinantly expressed and human liver microsomal cytochrome P450 2C9: Systematic determination of Inter System Extrapolation Factors. Xenobiotica (Submitted for publication).
  • Dai Y, Hebert MF, Isoherranen N, Davis CL, Marsh C, Shen DD, Thummel KE. (2006). Effect of CYP3A5 polymorphism on tacrolimus metabolic clearance in vitro. Drug Metab Dispos 34:836–847.
  • Darwish M, Kirby M, Robertson P Jr, Hellriegel ET. (2008). Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects. Clin Pharmacokinet 47:61–74.
  • Department of Health. (2010). NHS Information Centre Health Survey for England. Available from: http://www.dh.gov.uk/en/Publicationsandstatistics/PublishedSurvey/HealthSurveyForEngland/DH_632. Accessed October 2010.
  • Derry CL, Kroboth PD, Pittenger AL, Kroboth FJ, Corey SE, Smith RB. (1995). Pharmacokinetics and pharmacodynamics of triazolam after two intermittent doses in obese and normal-weight men. J Clin Psychopharmacol 15:197–205.
  • Dorne JL, Walton K, Renwick AG. (2003). Human variability in CYP3A4 metabolism and CYP3A4-related uncertainty factors for risk assessment. Food Chem Toxicol 41:201–224.
  • Eap CB, Buclin T, Cucchia G, Zullino D, Hustert E, Bleiber G, Golay KP, Aubert AC, Baumann P, Telenti A, Kerb R. (2004). Oral administration of a low dose of midazolam (75 microg) as an in vivo probe for CYP3A activity. Eur J Clin Pharmacol 60:237–246.
  • Eberts FS Jr, Philopoulos Y, Reineke LM, Vliek RW. (1981). Triazolam disposition. Clin Pharmacol Ther 29:81–93.
  • Edwards RJ, Adams DA, Watts PS, Davies DS, Boobis AR. (1998). Development of a comprehensive panel of antibodies against the major xenobiotic metabolising forms of cytochrome P450 in humans. Biochem Pharmacol 56:377–387.
  • Eeckhoudt SL, Desager JP, Robert AR, Leclercq I, Verbeeck RK, Horsmans Y. (2001). Midazolam and cortisol metabolism before and after CYP3A induction in humans. Int J Clin Pharmacol Ther 39:293–299.
  • Einolf HJ. (2007). Comparison of different approaches to predict metabolic drug-drug interactions. Xenobiotica 37:1257–1294.
  • Ellinwood EH Jr, Heatherly DG, Nikaido AM, Bjornsson TD, Kilts C. (1985). Comparative pharmacokinetics and pharmacodynamics of lorazepam, alprazolam and diazepam. Psychopharmacology (Berl) 86:392–399.
  • Emoto C, Iwasaki K. (2006). Enzymatic characteristics of CYP3A5 and CYP3A4: a comparison of in vitro kinetic and drug-drug interaction patterns. Xenobiotica 36:219–233.
  • Emoto C, Iwasaki K. (2007a). Approach to predict the contribution of cytochrome P450 enzymes to drug metabolism in the early drug-discovery stage: the effect of the expression of cytochrome b(5) with recombinant P450 enzymes. Xenobiotica 37:986–999.
  • Emoto C, Iwasaki K. (2007b). Relative roles of CYP2C19 and CYP3A4/5 in midazolam 1’-hydroxylation. Xenobiotica 37:592–603.
  • Emoto C, Murase S, Sawada Y, Jones BC, Iwasaki K. (2003). In vitro inhibitory effect of 1-aminobenzotriazole on drug oxidations catalyzed by human cytochrome P450 enzymes: a comparison with SKF-525A and ketoconazole. Drug Metab Pharmacokinet 18:287–295.
  • Farkas D, Oleson LE, Zhao Y, Harmatz JS, Zinny MA, Court MH, Greenblatt DJ. (2007). Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice. J Clin Pharmacol 47:286–294.
  • Fayer JL, Zannikos PN, Stevens JC, Luo Y, Sidhu R, Kirkesseli S. (2001). Lack of correlation between in vitro inhibition of CYP3A-mediated metabolism by a PPAR-gamma agonist and its effect on the clinical pharmacokinetics of midazolam, an in vivo probe of CYP3A activity. J Clin Pharmacol 41:305–316.
  • Fleishaker JC, Hulst LK. (1994). A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. Eur J Clin Pharmacol 46:35–39.
  • Fleishaker JC, Phillips JP, Eller MG, Smith RB. (1989). Pharmacokinetics and pharmacodynamics of alprazolam following single and multiple oral doses of a sustained-release formulation. J Clin Pharmacol 29:543–549.
  • Fraser AD. (1987). Urinary screening for alprazolam, triazolam, and their metabolites with the EMIT d.a.u. benzodiazepine metabolite assay. J Anal Toxicol 11:263–266.
  • Fraser AD, Bryan W, Isner AF. (1991). Urinary screening for alprazolam and its major metabolites by the Abbott ADx and TDx analyzers with confirmation by GC/MS. J Anal Toxicol 15:25–29.
  • Galetin A, Brown C, Hallifax D, Ito K, Houston JB. (2004). Utility of recombinant enzyme kinetics in prediction of human clearance: impact of variability, CYP3A5, and CYP2C19 on CYP3A4 probe substrates. Drug Metab Dispos 32:1411–1420.
  • Galetin A, Houston JB. (2006). Intestinal and hepatic metabolic activity of five cytochrome P450 enzymes: impact on prediction of first-pass metabolism. J Pharmacol Exp Ther 318:1220–1229.
  • Gertz M, Harrison A, Houston JB, Galetin A. (2010). Prediction of human intestinal first-pass metabolism of 25 CYP3A substrates from in vitro clearance and permeability data. Drug Metab Dispos 38:1147–1158.
  • Ghobadi C, Johnson TN, Aarabi M, Rowland-Yeo K, Jamei M, Rostami-Hodjegan A. (2010). Assessment of pharmacokinetics in obese patients. Part I. Clearance. Clin Pharmacokinet ( in press).
  • Glue P, Fang A, Gandelman K, Klee B. (2006). Pharmacokinetics of an extended release formulation of alprazolam (Xanax XR) in healthy normal adolescent and adult volunteers. Am J Ther 13:418–422.
  • Gorski JC, Huang SM, Pinto A, Hamman MA, Hilligoss JK, Zaheer NA, Desai M, Miller M, Hall SD. (2004). The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clin Pharmacol Ther 75:89–100.
  • Gorski JC, Vannaprasaht S, Hamman MA, Ambrosius WT, Bruce MA, Haehner-Daniels B, Hall SD. (2003). The effect of age, sex, and rifampin administration on intestinal and hepatic cytochrome P450 3A activity. Clin Pharmacol Ther 74:275–287.
  • Greenblatt DJ, Abernethy DR, Locniskar A, Harmatz JS, Limjuco RA, Shader RI. (1984). Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology 61:27–35.
  • Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, Shader RI. (1983a). Reduced clearance of triazolam in old age: relation to antipyrine oxidizing capacity. Br J Clin Pharmacol 15:303–309.
  • Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, Shader RI. (1983b). Alprazolam kinetics in the elderly. Relation to antipyrine disposition. Arch Gen Psychiatry 40:287–290.
  • Greenblatt DJ, Ehrenberg BL, Culm KE, Scavone JM, Corbett KE, Friedman HL, Harmatz JS, Shader RI. (2004). Kinetics and EEG effects of midazolam during and after 1-minute, 1-hour, and 3-hour intravenous infusions. J Clin Pharmacol 44:605–611.
  • Greenblatt DJ, Harmatz JS, Dorsey C, Shader RI. (1988). Comparative single-dose kinetics and dynamics of lorazepam, alprazolam, prazepam, and placebo. Clin Pharmacol Ther 44:326–334.
  • Greenblatt DJ, von Moltke LL, Harmatz JS, Counihan M, Graf JA, Durol AL, Mertzanis P, Duan SX, Wright CE, Shader RI. (1998b). Inhibition of triazolam clearance by macrolide antimicrobial agents: in vitro correlates and dynamic consequences. Clin Pharmacol Ther 64:278–285.
  • Greenblatt DJ, von Moltke LL, Harmatz JS, Durol AL, Daily JP, Graf JA, Mertzanis P, Hoffman JL, Shader RI. (2000). Alprazolam-ritonavir interaction: implications for product labeling. Clin Pharmacol Ther 67:335–341.
  • Greenblatt DJ, Wright CE, von Moltke LL, Harmatz JS, Ehrenberg BL, Harrel LM, Corbett K, Counihan M, Tobias S, Shader RI. (1998a). Ketoconazole inhibition of triazolam and alprazolam clearance: differential kinetic and dynamic consequences. Clin Pharmacol Ther 64:237–247.
  • Guyton AC, Hall JE. (2006). Textbook of Medical Physiology. Philadelphia, PA: Elsevier Inc.
  • Hallifax D, Foster JA, Houston JB. (2010). Prediction of human metabolic clearance from in vitro systems: retrospective analysis and prospective view. Pharm Res 27:2150–2161.
  • Heizmann P, Eckert M, Ziegler WH. (1983). Pharmacokinetics and bioavailability of midazolam in man. Br J Clin Pharmacol 16 Suppl 1:43S–49S.
  • Hesselink DA, van Schaik RH, van der Heiden IP, van der Werf M, Gregoor PJ, Lindemans J, Weimar W, van Gelder T. (2003). Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther 74:245–254.
  • Hirota N, Ito K, Iwatsubo T, Green CE, Tyson CA, Shimada N, Suzuki H, Sugiyama Y. (2001). In vitro/in vivo scaling of alprazolam metabolism by CYP3A4 and CYP3A5 in humans. Biopharm Drug Dispos 22:53–71.
  • Houston JB, Carlile DJ. (1997). Incorporation of in vitro drug metabolism data into physiologically-based pharmacokinetic models. Toxicol In Vitro 11:473–478.
  • Houston JB, Galetin A. (2008). Methods for predicting in vivo pharmacokinetics using data from in vitro assays. Curr Drug Metab 9:940–951.
  • Howgate EM, Rowland Yeo K, Proctor NJ, Tucker GT, Rostami-Hodjegan A. (2006). Prediction of in vivo drug clearance from in vitro data. I: impact of inter-individual variability. Xenobiotica 36:473–497.
  • Huang W, Lin YS, McConn DJ 2nd, Calamia JC, Totah RA, Isoherranen N, Glodowski M, Thummel KE. (2004). Evidence of significant contribution from CYP3A5 to hepatic drug metabolism. Drug Metab Dispos 32:1434–1445.
  • Hustert E, Haberl M, Burk O, Wolbold R, He YQ, Klein K, Nuessler AC, Neuhaus P, Klattig J, Eiselt R, Koch I, Zibat A, Brockmöller J, Halpert JR, Zanger UM, Wojnowski L. (2001). The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 11:773–779.
  • Hyland R, Osborne T, Payne A, Kempshall S, Logan YR, Ezzeddine K, Jones B. (2009). In vitro and in vivo glucuronidation of midazolam in humans. Br J Clin Pharmacol 67:445–454.
  • Ibrahim A, Karim A, Feldman J, Kharasch E. (2002). The influence of parecoxib, a parenteral cyclooxygenase-2 specific inhibitor, on the pharmacokinetics and clinical effects of midazolam. Anesth Analg 95:667–73, table of contents.
  • Ito T, Kato M, Chiba K, Okazaki O, Sugiyama Y. (2010). Estimation of the interindividual variability of cytochrome 2D6 activity from urinary metabolic ratios in the literature. Drug Metab Pharmacokinet 25:243–253.
  • Jamei M, Marciniak S, Feng K, Barnett A, Tucker G, Rostami-Hodjegan A. (2009). The Simcyp population-based ADME simulator. Expert Opin Drug Metab Toxicol 5:211–223.
  • Johnson TN, Tucker GT, Tanner MS, Rostami-Hodjegan A. (2005). Changes in liver volume from birth to adulthood: a meta-analysis. Liver Transpl 11:1481–1493.
  • Kharasch ED, Walker A, Hoffer C, Sheffels P. (2004). Intravenous and oral alfentanil as in vivo probes for hepatic and first-pass cytochrome P450 3A activity: noninvasive assessment by use of pupillary miosis. Clin Pharmacol Ther 76:452–466.
  • Kim KA, Park PW, Lee OJ, Kang DK, Park JY. (2007). Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects. J Clin Pharmacol 47:87–93.
  • Kinirons MT, O’Shea D, Kim RB, Groopman JD, Thummel KE, Wood AJ, Wilkinson GR. (1999). Failure of erythromycin breath test to correlate with midazolam clearance as a probe of cytochrome P4503A. Clin Pharmacol Ther 66:224–231.
  • Kirby BJ, Unadkat JD. (2010). Impact of ignoring extraction ratio when predicting drug-drug interactions, fraction metabolized, and intestinal first-pass contribution. Drug Metab Dispos 38:1926–1933.
  • Klotz U, Ziegler G. (1982). Physiologic and temporal variation in hepatic elimination of midazolam. Clin Pharmacol Ther 32:107–112.
  • Kroboth PD, McAuley JW, Kroboth FJ, Bertz RJ, Smith RB. (1995). Triazolam pharmacokinetics after intravenous, oral, and sublingual administration. J Clin Psychopharmacol 15:259–262.
  • Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J, Watkins PB, Daly A, Wrighton SA, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Venkataramanan R, Strom S, Thummel K, Boguski MS, Schuetz E. (2001). Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 27:383–391.
  • Kupferschmidt HH, Ha HR, Ziegler WH, Meier PJ, Krähenbühl S. (1995). Interaction between grapefruit juice and midazolam in humans. Clin Pharmacol Ther 58:20–28.
  • Lam YW, Alfaro CL, Ereshefsky L, Miller M. (2003). Pharmacokinetic and pharmacodynamic interactions of oral midazolam with ketoconazole, fluoxetine, fluvoxamine, and nefazodone. J Clin Pharmacol 43:1274–1282.
  • Lamba V, Panetta JC, Strom S, Schuetz EG. (2010). Genetic predictors of interindividual variability in hepatic CYP3A4 expression. J Pharmacol Exp Ther 332:1088–1099.
  • Liangpunsakul S, Kolwankar D, Pinto A, Gorski JC, Hall SD, Chalasani N. (2005). Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: a comparison with nonalcoholics. Hepatology 41:1144–1150.
  • Lin KM, Lau JK, Smith R, Phillips P, Antal E, Poland RE. (1988). Comparison of alprazolam plasma levels in normal Asian and Caucasian male volunteers. Psychopharmacology (Berl) 96:365–369.
  • Mandema JW, Tuk B, van Steveninck AL, Breimer DD, Cohen AF, Danhof M. (1992). Pharmacokinetic-pharmacodynamic modeling of the central nervous system effects of midazolam and its main metabolite alpha-hydroxymidazolam in healthy volunteers. Clin Pharmacol Ther 51:715–728.
  • Masica AL, Mayo G, Wilkinson GR. (2004). In vivo comparisons of constitutive cytochrome P450 3A activity assessed by alprazolam, triazolam, and midazolam. Clin Pharmacol Ther 76:341–349.
  • Moschitto LJ, Greenblatt DJ. (1983). Concentration-independent plasma protein binding of benzodiazepines. J Pharm Pharmacol 35:179–180.
  • Nakajima M, Tane K, Nakamura S, Shimada N, Yamazaki H, Yokoi T. (2002). Evaluation of approach to predict the contribution of multiple cytochrome P450s in drug metabolism using relative activity factor: effects of the differences in expression levels of NADPH-cytochrome P450 reductase and cytochrome b(5) in the expression system and the differences in the marker activities. J Pharm Sci 91:952–963.
  • Obach RS. (1999). 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 Metab Dispos 27:1350–1359.
  • Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F, Rance DJ, Wastall P. (1997). The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J Pharmacol Exp Ther 283:46–58.
  • Ochs HR, Greenblatt DJ, Labedzki L, Smith RB. (1986). Alprazolam kinetics in patients with renal insufficiency. J Clin Psychopharmacol 6:292–294.
  • Olkkola KT, Ahonen J, Neuvonen PJ. (1996). The effects of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth Analg 82:511–516.
  • Olkkola KT, Aranko K, Luurila H, Hiller A, Saarnivaara L, Himberg JJ, Neuvonen PJ. (1993). A potentially hazardous interaction between erythromycin and midazolam. Clin Pharmacol Ther 53:298–305.
  • Paine MF, Khalighi M, Fisher JM, Shen DD, Kunze KL, Marsh CL, Perkins JD, Thummel KE. (1997). Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther 283:1552–1562.
  • Pourbaix S, Desager JP, Hulhoven R, Smith RB, Harvengt C. (1985). Pharmacokinetic consequences of long term coadministration of cimetidine and triazolobenzodiazepines, alprazolam and triazolam, in healthy subjects. Int J Clin Pharmacol Ther Toxicol 23:447–451.
  • Proctor NJ, Tucker GT, Rostami-Hodjegan A. (2004). Predicting drug clearance from recombinantly expressed CYPs: intersystem extrapolation factors. Xenobiotica 34:151–178.
  • Qiu H, Mathäs M, Nestler S, Bengel C, Nem D, Gödtel-Armbrust U, Lang T, Taudien S, Burk O, Wojnowski L. (2010). The unique complexity of the CYP3A4 upstream region suggests a nongenetic explanation of its expression variability. Pharmacogenet Genomics 20:167–178.
  • Rawden HC, Carlile DJ, Tindall A, Hallifax D, Galetin A, Ito K, Houston JB. (2005). Microsomal prediction of in vivo clearance and associated interindividual variability of six benzodiazepines in humans. Xenobiotica 35:603–625.
  • Rostami-Hodjegan A, Tucker GT. (2007). Simulation and prediction of in vivo drug metabolism in human populations from in vitro data. Nat Rev Drug Discov 6:140–148.
  • Rowland Yeo K, Rostami-Hodjegan A, Tucker GT. (2004). Abundance of cytochromes P450 in human liver: a meta analysis. Br J Clin Pharmacol, 57:687.
  • Scavone JM, Greenblatt DJ, Friedman H, Shader RI. (1986). Enhanced bioavailability of triazolam following sublingual versus oral administration. J Clin Pharmacol 26:208–210.
  • Scavone JM, Greenblatt DJ, Locniskar A, Shader RI. (1988). Alprazolam pharmacokinetics in women on low-dose oral contraceptives. J Clin Pharmacol 28:454–457.
  • Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. (1994). Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414–423.
  • Smith RB, Kroboth PD. (1987). Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects. Psychopharmacology (Berl) 93:105–112.
  • Smith RB, Kroboth PD, Vanderlugt JT, Phillips JP, Juhl RP. (1984). Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration. Psychopharmacology (Berl) 84:452–456.
  • Soars MG, Grime K, Riley RJ. (2006). Comparative analysis of substrate and inhibitor interactions with CYP3A4 and CYP3A5. Xenobiotica 36:287–299.
  • Stringer RA, Strain-Damerell C, Nicklin P, Houston JB. (2009). Evaluation of recombinant cytochrome P450 enzymes as an in vitro system for metabolic clearance predictions. Drug Metab Dispos 37:1025–1034.
  • Tateishi T, Watanabe M, Nakura H, Asoh M, Shirai H, Mizorogi Y, Kobayashi S, Thummel KE, Wilkinson GR. (2001). CYP3A activity in European American and Japanese men using midazolam as an in vivo probe. Clin Pharmacol Ther 69:333–339.
  • Thummel KE, O’Shea D, Paine MF, Shen DD, Kunze KL, Perkins JD, Wilkinson GR. (1996). Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin Pharmacol Ther 59:491–502.
  • Tsunoda SM, Velez RL, von Moltke LL, Greenblatt DJ. (1999). Differentiation of intestinal and hepatic cytochrome P450 3A activity with use of midazolam as an in vivo probe: effect of ketoconazole. Clin Pharmacol Ther 66:461–471.
  • Varhe A, Olkkola KT, Neuvonen PJ. (1996). Diltiazem enhances the effects of triazolam by inhibiting its metabolism. Clin Pharmacol Ther 59:369–375.
  • Venkatakrishnan K, Culm KE, Ehrenberg BL, Harmatz JS, Corbett KE, Fleishaker JC, Greenblatt DJ. (2005). Kinetics and dynamics of intravenous adinazolam, N-desmethyl adinazolam, and alprazolam in healthy volunteers. J Clin Pharmacol 45:529–537.
  • Villikka K, Kivistö KT, Backman JT, Olkkola KT, Neuvonen PJ. (1997). Triazolam is ineffective in patients taking rifampin. Clin Pharmacol Ther 61:8–14.
  • Vinik HR, Reves JG, Greenblatt DJ, Abernethy DR, Smith LR. (1983). The pharmacokinetics of midazolam in chronic renal failure patients. Anesthesiology 59:390–394.
  • von Richter O, Glavinas H, Krajcsi P, Liehner S, Siewert B, Zech K. (2009). A novel screening strategy to identify ABCB1 substrates and inhibitors. Naunyn Schmiedebergs Arch Pharmacol 379:11–26.
  • Walsky RL, Obach RS. (2004). Validated assays for human cytochrome P450 activities. Drug Metab Dispos 32:647–660.
  • Wandel C, Witte JS, Hall JM, Stein CM, Wood AJ, Wilkinson GR. (2000). CYP3A activity in African American and European American men: population differences and functional effect of the CYP3A4*1B5’-promoter region polymorphism. Clin Pharmacol Ther 68:82–91.
  • Weaver R, Graham KS, Beattie IG, Riley RJ. (2003). Cytochrome P450 inhibition using recombinant proteins and mass spectrometry/multiple reaction monitoring technology in a cassette incubation. Drug Metab Dispos 31:955–966.
  • Westlind-Johnsson A, Malmebo S, Johansson A, Otter C, Andersson TB, Johansson I, Edwards RJ, Boobis AR, Ingelman-Sundberg M. (2003). Comparative analysis of CYP3A expression in human liver suggests only a minor role for CYP3A5 in drug metabolism. Drug Metab Dispos 31:755–761.
  • Wienkers LC, Heath TG. (2005). Predicting in vivo drug interactions from in vitro drug discovery data. Nat Rev Drug Discov 4:825–833.
  • Wilkinson GR, Shand DG. (1975). Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther 18:377–390.
  • Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA. (2002). Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos 30:883–891.
  • Wilson ZE, Rostami-Hodjegan A, Burn JL, Tooley A, Boyle J, Ellis SW, Tucker GT. (2003). Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver. Br J Clin Pharmacol 56:433–440.
  • Wright CE, Sisson TL, Fleishaker JC, Antal EJ. (1997). Pharmacokinetics and psychomotor performance of alprazolam: concentration-effect relationship. J Clin Pharmacol 37:321–329.
  • Yang J, Jamei M, Yeo KR, Tucker GT, Rostami-Hodjegan A. (2007). Prediction of intestinal first-pass drug metabolism. Curr Drug Metab 8:676–684.
  • Zhang X, Quinney SK, Gorski JC, Jones DR, Hall SD. (2009). Semiphysiologically based pharmacokinetic models for the inhibition of midazolam clearance by diltiazem and its major metabolite. Drug Metab Dispos 37:1587–1597.

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