937
Views
44
CrossRef citations to date
0
Altmetric
Review

CYP3A activity: towards dose adaptation to the individual

ORCID Icon, ORCID Icon & ORCID Icon
Pages 479-497 | Received 17 Jul 2015, Accepted 04 Mar 2016, Published online: 26 Mar 2016

References

  • Stoll F, Burhenne J, Lausecker B, et al. Reduced exposure variability of the CYP3A substrate simvastatin by dose individualization to CYP3A activity. J Clin Pharmacol. 2013;53:1199–1204.
  • Zhou SF. Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab. 2008;9:310–322.
  • Backman JT, Kivistö KT, Olkkola KT, et al. 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. 1998;54:53–58.
  • US Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for industry drug interaction studies – study design, data analysis, implications for dosing, and labeling recommendations; 2012 [cited 2015 Jul 13]. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm292362.pdf
  • Varma MV, Feng B, Obach RS, et al. Physicochemical determinants of human renal clearance. J Med Chem. 2009;52:4844–4852.
  • Nebert DW, Nelson DR, Coon MJ, et al. The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol. 1991;10:1–14.
  • Daly AK. Significance of the minor cytochrome P450 3A isoforms. Clin Pharmacokinet. 2006;45:13–31.
  • Shin KH, Choi MH, Lim KS, et al. Evaluation of endogenous metabolic markers of hepatic CYP3A activity using metabolic profiling and midazolam clearance. Clin Pharmacol Ther. 2013;94:601–609.
  • Hisaka A, Nakamura M, Tsukihashi A, et al. Assessment of intestinal availability (FG) of substrate drugs of cytochrome p450s by analyzing changes in pharmacokinetic properties caused by drug-drug interactions. Drug Metab Dispos. 2014;42:1640–1645.
  • Fuhr U, Jetter A, Kirchheiner J. Appropriate phenotyping procedures for drug metabolizing enzymes and transporters in humans and their simultaneous use in the “cocktail” approach. Clin Pharmacol Ther. 2007;81:270–283.
  • Labroo RB, Thummel KE, Kunze KL, et al. Catalytic role of cytochrome P4503A4 in multiple pathways of alfentanil metabolism. Drug Metab Dispos. 1995;23:490–496.
  • Kharasch ED, Vangveravong S, Buck N, et al. Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil. Clin Pharmacol Ther. 2011;89:562–570.
  • Kharasch ED, Walker A, Hoffer C, et al. Sensitivity of intravenous and oral alfentanil and pupillary miosis as minimally invasive and noninvasive probes for hepatic and first-pass CYP3A activity. J Clin Pharmacol. 2005;45:1187–1197.
  • Kharasch ED, Francis A, London A, et al. Sensitivity of intravenous and oral alfentanil and pupillary miosis as minimal and noninvasive probes for hepatic and first-pass CYP3A induction. Clin Pharmacol Ther. 2011;90:100–108.
  • Chaobal HN, Kharasch ED. Single-point sampling for assessment of constitutive, induced, and inhibited cytochrome P450 3A activity with alfentanil or midazolam. Clin Pharmacol Ther. 2005;78:529–539.
  • Baririan N, Van Obbergh L, Desager JP, et al. Alfentanil-induced miosis as a surrogate measure of alfentanil pharmacokinetics in patients with mild and moderate liver cirrhosis. Clin Pharmacokinet. 2007;46:261–270.
  • Gorski JC, Jones DR, Hamman MA, et al. Biotransformation of alprazolam by members of the human cytochrome P4503A subfamily. Xenobiotica. 1999;29:931–944.
  • Schmider J, Brockmöller J, Arold G, et al. Simultaneous assessment of CYP3A4 and CYP1A2 activity in vivo with alprazolam and caffeine. Pharmacogenetics. 1999;9:725–734.
  • Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Alprazolam-ritonavir interaction: implications for product labeling. Clin Pharmacol Ther. 2000;67:335–341.
  • Furukori H, Otani K, Yasui N, et al. Effect of carbamazepine on the single oral dose pharmacokinetics of alprazolam. Neuropsychopharmacology. 1998;18:364–369.
  • Wennerholm A, Allqvist A, Svensson JO, et al. Alprazolam as a probe for CYP3A using a single blood sample: pharmacokinetics of parent drug, and of alpha- and 4-hydroxy metabolites in healthy subjects. Eur J Clin Pharmacol. 2005;61:113–118.
  • Masica AL, Mayo G, Wilkinson GR. In vivo comparisons of constitutive cytochrome P450 3A activity assessed by alprazolam, triazolam, and midazolam. Clin Pharmacol Ther. 2004;76:341–349.
  • Park JY, Kim KA, Park PW, et al. Effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy subjects. Clin Pharmacol Ther. 2006;79:590–599.
  • Zhu M, Zhao W, Jimenez H, et al. Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes. Drug Metab Dispos. 2005;33:500–507.
  • Lamberg TS, Kivistö KT, Neuvonen PJ. Concentrations and effects of buspirone are considerably reduced by rifampicin. Br J Clin Pharmacol. 1998;45:381–385.
  • Kivistö KT, Lamberg TS, Kantola T, et al. Plasma buspirone concentrations are greatly increased by erythromycin and itraconazole. Clin Pharmacol Ther. 1997;62:348–354.
  • Lilja JJ, Kivistö KT, Backman JT, et al. Grapefruit juice substantially increases plasma concentrations of buspirone. Clin Pharmacol Ther. 1998;64:655–660.
  • Thummel KE, Shen DD, Podoll TD, et al. Use of midazolam as a human cytochrome P450 3A probe: I. In vitro-in vivo correlations in liver transplant patients. J Pharmacol Exp Ther. 1994;271:549–556.
  • Thummel KE, Shen DD, Podoll TD, et al. Use of midazolam as a human cytochrome P450 3A probe: II. Characterization of inter- and intraindividual hepatic CYP3A variability after liver transplantation. J Pharmacol Exp Ther. 1994;271:557–566.
  • Hohmann N, Kocheise F, Carls A, et al. Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A activity in humans. Br J Clin Pharmacol. 2015;79:278–285.
  • Streetman DS, Kashuba AD, Bertino JS Jr, et al. Use of midazolam urinary metabolic ratios for cytochrome P450 3A (CYP3A) phenotyping. Pharmacogenetics. 2001;11:349–355.
  • Krishna G, Moton A, Ma L, et al. Effects of oral posaconazole on the pharmacokinetic properties of oral and intravenous midazolam: a phase I, randomized, open-label, crossover study in healthy volunteers. Clin Ther. 2009;31:286–298.
  • Backman JT, Olkkola KT, Neuvonen PJ. Rifampin drastically reduces plasma concentrations and effects of oral midazolam. Clin Pharmacol Ther. 1996;59:7–13.
  • European Medicines Agency. Guideline on the investigation of drug interactions; 2012 [cited 2015 July 13]. Available from: www.ema.europa.eu/ema/pages/includes/document/open_document.jsp?webContentId=WC500129606
  • Kim JS, Nafziger AN, Tsunoda SM, et al. Limited sampling strategy to predict AUC of the CYP3A phenotyping probe midazolam in adults: application to various assay techniques. J Clin Pharmacol. 2002;42:376–382.
  • Katzenmaier S, Markert C, Riedel KD, et al. Determining the time course of CYP3A inhibition by potent reversible and irreversible CYP3A inhibitors using A limited sampling strategy. Clin Pharmacol Ther. 2011;90:666–673.
  • Mueller SC, Drewelow B. Evaluation of limited sampling models for prediction of oral midazolam AUC for CYP3A phenotyping and drug interaction studies. Eur J Clin Pharmacol. 2013;69:1127–1134.
  • Nguyen AN, Hoffman JT, Tsunoda SM, et al. Evaluation of intravenous midazolam limited sampling models to determine area under the concentration time curve during cytochrome P450 3A baseline, inhibition and induction or activation. Int J Clin Pharmacol Ther. 2012;50:468–475.
  • Tai W, Gong SL, Tsunoda SM, et al. Evaluation of partial area under the concentration time curve to estimate midazolam apparent oral clearance for cytochrome P450 3A phenotyping. Drug Metabol Drug Interact. 2013;28:217–223.
  • Masters JC, Harano DM, Greenberg HE, et al. Limited sampling strategy of partial area under the concentration-time curves to estimate midazolam systemic clearance for cytochrome P450 3A phenotyping. Ther Drug Monit. 2015;37:84–89.
  • Lin YS, Lockwood GF, Graham MA, et al. In-vivo phenotyping for CYP3A by a single-point determination of midazolam plasma concentration. Pharmacogenetics. 2001;11:781–791.
  • Penzak SR, Busse KH, Robertson SM, et al. Limitations of using a single postdose midazolam concentration to predict CYP3A-mediated drug interactions. J Clin Pharmacol. 2008;48:671–680.
  • Rogers JF, Nafziger AN, Kashuba AD, et al. Single plasma concentrations of 1ʹ-hydroxymidazolam or the ratio of 1ʹ-hydroxymidazolam: midazolamdo not predict midazolam clearance in healthy subjects. J Clin Pharmacol. 2002;42:1079–1082.
  • Lee JI, Chaves-Gnecco D, Amico JA, et al. Application of semisimultaneous midazolam administration for hepatic and intestinal cytochrome P450 3A phenotyping. Clin Pharmacol Ther. 2002;72:718–728.
  • Lappin G, Rowland M, Garner RC. The use of isotopes in the determination of absolute bioavailability of drugs in humans. Expert Opin Drug Metab Toxicol. 2006;2:419–427.
  • Halama B, Hohmann N, Burhenne J, et al. A nanogram dose of the CYP3A probe substrate midazolam to evaluate drug interactions. Clin Pharmacol Ther. 2013;93:564–571.
  • de Wildt SN, Ito S, Koren G. Challenges for drug studies in children: CYP3A phenotyping as example. Drug Discov Today. 2009;14:6–15.
  • Hohmann N, Halama B, Siller N, et al. Response to “can CYP3A activity be evaluated for drug interaction using a nanogram dose of probe drug?”: evaluation of CYP3A activity with microdoses of midazolam. Clin Pharmacol Ther. 2014;95:490–491.
  • Kronbach T, Mathys D, Umeno M, et al. Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Mol Pharmacol. 1989;36:89–96.
  • Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Differential impairment of triazolam and zolpidem clearance by ritonavir. J Acquir Immune Defic Syndr. 2000;24:129–136.
  • Villikka K, Kivistö KT, Backman JT, et al. Triazolam is ineffective in patients taking rifampin. Clin Pharmacol Ther. 1997;61:8–14.
  • Tomalik-Scharte D, Lütjohann D, Doroshyenko O, et al. Plasma 4beta-hydroxycholesterol: an endogenous CYP3A metric? Clin Pharmacol Ther. 2009;86:147–153.
  • Kasichayanula S, Boulton DW, Luo WL, et al. Validation of 4β-hydroxycholesterol and evaluation of other endogenous biomarkers for the assessment of CYP3A activity in healthy subjects. Br J Clin Pharmacol. 2014;78:1122–1134.
  • Peng CC, Templeton I, Thummel KE, et al. Evaluation of 6β-hydroxycortisol, 6β-hydroxycortisone, and a combination of the two as endogenous probes for inhibition of CYP3A4 in vivo. Clin Pharmacol Ther. 2011;89:888–895.
  • Ushiama H, Echizen H, Nachi S, et al. Dose-dependent inhibition of CYP3A activity by clarithromycin during helicobacter pylori eradication therapy assessed by changes in plasma lansoprazole levels and partial cortisol clearance to 6beta-hydroxycortisol. Clin Pharmacol Ther. 2002;72:33–43.
  • Furuta T, Suzuki A, Mori C, et al. Evidence for the validity of cortisol 6 beta-hydroxylation clearance as a new index for in vivo cytochrome P450 3A phenotyping in humans. Drug Metab Dispos. 2003;31:1283–1287.
  • Fleishaker JC, Pearson PG, Wienkers LC, et al. Biotransformation of tirilazad in human: 2. Effect of ketoconazole on tirilazad clearance and oral bioavailability. J Pharmacol Exp Ther. 1996;277:991–998.
  • Gass RJ, Gal J, Fogle PW, et al. Neither dapsone hydroxylation nor cortisol 6beta-hydroxylation detects the inhibition of CYP3A4 by HIV-1 protease inhibitors. Eur J Clin Pharmacol. 1998;54:741–747.
  • Chen YC, Gotzkowsky SK, Nafziger AN, et al. Poor correlation between 6beta-hydroxycortisol: cortisolmolar ratios and midazolam clearance as measure of hepatic CYP3A activity. Br J Clin Pharmacol. 2006;62:187–195.
  • Chung E, Nafziger AN, Kazierad DJ, et al. Comparison of midazolam and simvastatin as cytochrome P450 3A probes. Clin Pharmacol Ther. 2006;79:350–361.
  • Hyland R, Roe EG, Jones BC, et al. Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol. 2001;51:239–248.
  • Muirhead GJ, Wulff MB, Fielding A, et al. Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir. Br J Clin Pharmacol. 2000;50:99–107.
  • Jalava KM, Olkkola KT, Neuvonen PJ. Itraconazole greatly increases plasma concentrations and effects of felodipine. Clin Pharmacol Ther. 1997;61:410–415.
  • Bailey DG, Bend JR, Arnold JM, et al. Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice. Clin Pharmacol Ther. 1996;60:25–33.
  • Lundahl J, Regårdh CG, Edgar B, et al. Effects of grapefruit juice ingestion–pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Eur J Clin Pharmacol. 1997;52:139–145.
  • Snyder BD, Rowland A, Polasek TM, et al. Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions. Eur J Clin Pharmacol. 2014;70:1115–1122.
  • Mirghani RA, Ericsson O, Tybring G, et al. Quinine 3-hydroxylation as a biomarker reaction for the activity of CYP3A4 in man. Eur J Clin Pharmacol. 2003;59:23–28.
  • Björkhem-Bergman L, Bäckström T, Nylén H, et al. Quinine compared to 4β-hydroxycholesterol and midazolam as markers for CYP3A induction by rifampicin. Drug Metab Pharmacokinet. 2014;29:352–355.
  • Mirghani RA, Hellgren U, Bertilsson L, et al. Metabolism and elimination of quinine in healthy volunteers. Eur J Clin Pharmacol. 2003;59:423–427.
  • Nyunt MM, Lu Y, El-Gasim M, et al. Effects of ritonavir-boosted lopinavir on the pharmacokinetics of quinine. Clin Pharmacol Ther. 2012;91:889–895.
  • Chiou WL, Jeong HY, Wu TC, et al. Use of the erythromycin breath test for in vivo assessments of cytochrome P4503A activity and dosage individualization. Clin Pharmacol Ther. 2001;70:305–310.
  • Kurnik D, Wood AJ, Wilkinson GR. The erythromycin breath test reflects P-glycoprotein function independently of cytochrome P450 3A activity. Clin Pharmacol Ther. 2006;80:228–234.
  • Franke RM, Baker SD, Mathijssen RH, et al. Influence of solute carriers on the pharmacokinetics of CYP3A4 probes. Clin Pharmacol Ther. 2008;84:704–709.
  • Kuo BP, Hu OY, Hsiong CH, et al. Single-point plasma or urine dextromethorphan method for determining CYP3A activity. Biopharm Drug Dispos. 2003;24:367–373.
  • Evans DC, O’Connor D, Lake BG, et al. Eletriptan metabolism by human hepatic CYP450 enzymes and transport by human P-glycoprotein. Drug Metab Dispos. 2003;31:861–869.
  • Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000;38:41–57.
  • Lin YS, Dowling AL, Quigley SD, et al. Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism. Mol Pharmacol. 2002;62:162–172.
  • Kharasch ED, Jubert C, Senn T, et al. Intraindividual variability in male hepatic CYP3A4 activity assessed by alfentanil and midazolam clearance. J Clin Pharmacol. 1999;39:664–669.
  • Kharasch ED, Russell M, Mautz D, et al. The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions. Anesthesiology. 1997;87:36–50.
  • Kashuba AD, Jr BJS, Rocci ML Jr, et al. Quantification of 3-month intraindividual variability and the influence of sex and menstrual cycle phase on CYP3A activity as measured by phenotyping with intravenous midazolam. Clin Pharmacol Ther. 1998;64:269–277.
  • Tomalik-Scharte D, Suleiman AA, Frechen S, et al. Population pharmacokinetic analysis of circadian rhythms in hepatic CYP3A activity using midazolam. J Clin Pharmacol. 2014;54:1162–1169.
  • Thirumaran RK, Lamba JK, Kim RB, et al. Intestinal CYP3A4 and midazolam disposition in vivo associate with VDR polymorphisms and show seasonal variation. Biochem Pharmacol. 2012;84:104–112.
  • Ma JD, Nafziger AN, Mylott W, et al. Lack of effect of subject posture on intravenous midazolam clearance: implications for hepatic cytochrome P450 3A phenotyping. Br J Clin Pharmacol. 2009;67:374–375.
  • Ohnhaus EE, Breckenridge AM, Park BK. Urinary excretion of 6 beta-hydroxycortisol and the time course measurement of enzyme induction in man. Eur J Clin Pharmacol. 1989;36:39–46.
  • Ohno Y, Hisaka A, Ueno M, et al. General framework for the prediction of oral drug interactions caused by CYP3A4 induction from in vivo information. Clin Pharmacokinet. 2008;47:669–680.
  • Mikati MA, Browne TR, Collins JF. Time course of carbamazepine autoinduction the VA cooperative study no.118 group. Neurology. 1989;39:592–594.
  • Imai H, Kotegawa T, Tsutsumi K, et al. The recovery time-course of CYP3A after induction by St John’s wort administration. Br J Clin Pharmacol. 2008;65:701–707.
  • Kroiss M, Quinkler M, Lutz WK, et al. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2011;75:585–591.
  • Keubler A, Weiss J, Haefeli WE, et al. Drug interaction of efavirenz and midazolam: efavirenz activates the CYP3A-mediated midazolam 1ʹ-hydroxylation in vitro. Drug Metab Dispos. 2012;40:1178–1182.
  • Saah AJ, Winchell GA, Nessly ML, et al. Pharmacokinetic profile and tolerability of indinavir-ritonavir combinations in healthy volunteers. Antimicrob Agents Chemother. 2001;45:2710–2715.
  • Okudaira T, Kotegawa T, Imai H, et al. Effect of the treatment period with erythromycin on cytochrome P450 3A activity in humans. J Clin Pharmacol. 2007;47:871–876.
  • Lilja JJ, Kivistö KT, Neuvonen PJ. Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Clin Pharmacol Ther. 2000;68:384–390.
  • Yang J, Liao M, Shou M, et al. Cytochrome p450 turnover: regulation of synthesis and degradation, methods for determining rates, and implications for the prediction of drug interactions. Curr Drug Metab. 2008;9:384–394.
  • Hulskotte E, Gupta S, Xuan F, et al. Pharmacokinetic interaction between the hepatitis C virus protease inhibitor boceprevir and cyclosporine and tacrolimus in healthy volunteers. Hepatology. 2012;56:1622–1630.
  • Saari TI, Laine K, Leino K, et al. Voriconazole, but not terbinafine, markedly reduces alfentanil clearance and prolongs its half-life. Clin Pharmacol Ther. 2006;80:502–508.
  • Lilja JJ, Kivistö KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther. 1998;64:477–483.
  • Hodgson E, Rose RL. Metabolic interactions of agrochemicals in humans. Pest Manag Sci. 2008;64:617–621.
  • Klein K, Zanger UM. Pharmacogenomics of cytochrome P450 3A4: recent progress toward the “Missing Heritability” problem. Front Genet. 2013;4:12.
  • Chen M, Nafziger AN, Bertino JS Jr. Drug-metabolizing enzyme inhibition by ketoconazole does not reduce interindividual variability of CYP3A activity as measured by oral midazolam. Drug Metab Dispos. 2006;34:2079–2082.
  • van Schaik RH, van der Heiden IP, van den Anker JN, et al. CYP3A5 variant allele frequencies in Dutch Caucasians. Clin Chem. 2002;48:1668–1671.
  • Birdwell KA, Decker B, Barbarino JM, et al. Clinical pharmacogenetics implementation consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin Pharmacol Ther. 2015;98:19–24.
  • Werk AN, Cascorbi I. Functional gene variants of CYP3A4. Clin Pharmacol Ther. 2014;96:340–348.
  • Werk AN, Lefeldt S, Bruckmueller H, et al. Identification and characterization of a defective CYP3A4 genotype in a kidney transplant patient with severely diminished tacrolimus clearance. Clin Pharmacol Ther. 2014;95:416–422.
  • Blake MJ, Castro L, Leeder JS, et al. Ontogeny of drug metabolizing enzymes in the neonate. Semin Fetal Neonatal Med. 2005;10:123–138.
  • Gorski JC, Vannaprasaht S, Hamman MA, et al. The effect of age, sex, and rifampin administration on intestinal and hepatic cytochrome P450 3A activity. Clin Pharmacol Ther. 2003;74:275–287.
  • Brill MJ, Van Rongen A, Houwink AP, et al. Midazolam pharmacokinetics in morbidly obese patients following semi-simultaneous oral and intravenous administration: a comparison with healthy volunteers. Clin Pharmacokinet. 2014;53:931–941.
  • Morón B, Verma AK, Das P, et al. CYP3A4-catalyzed simvastatin metabolism as a non-invasive marker of small intestinal health in celiac disease. Am J Gastroenterol. 2013;108:1344–1351.
  • Lang CC, Brown RM, Kinirons MT, et al. Decreased intestinal CYP3A in celiac disease: reversal after successful gluten-free diet: a potential source of interindividual variability in first-pass drug metabolism. Clin Pharmacol Ther. 1996;59:41–46.
  • Chan LN, Lin YS, Tay-Sontheimer JC, et al. Proximal Roux-en-Y gastric bypass alters drug absorption pattern but not systemic exposure of CYP3A4 and P-glycoprotein substrates. Pharmacotherapy. 2015;35:361–369.
  • Albarmawi A, Czock D, Gauss A, et al. CYP3A activity in severe liver cirrhosis correlates with Child-Pugh and model for end-stage liver disease (MELD) scores. Br J Clin Pharmacol. 2014;77:160–169.
  • Parkinson A, Mudra DR, Johnson C, et al. The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes. Toxicol Appl Pharmacol. 2004;199:193–209.
  • Kirwan CJ, MacPhee IA, Lee T, et al. Acute kidney injury reduces the hepatic metabolism of midazolam in critically ill patients. Intensive Care Med. 2012;38:76–84.
  • Morcos PN, Moreira SA, Brennan BJ, et al. Influence of chronic hepatitis C infection on cytochrome P450 3A4 activity using midazolam as an in vivo probe substrate. Eur J Clin Pharmacol. 2013;69:1777–1784.
  • Dostalek M, Court MH, Yan B, et al. Significantly reduced cytochrome P450 3A4 expression and activity in liver from humans with diabetes mellitus. Br J Pharmacol. 2011;163:937–947.
  • Dickmann LJ, Patel SK, Wienkers LC, et al. Effects of interleukin 1β (IL-1β) and IL-1β/interleukin 6 (IL-6) combinations on drug metabolizing enzymes in human hepatocyte culture. Curr Drug Metab. 2012;13:930–937.
  • Schmitt C, Kuhn B, Zhang X, et al. Disease-drug-drug interaction involving tocilizumab and simvastatin in patients with rheumatoid arthritis. Clin Pharmacol Ther. 2011;89:735–740.
  • Rivory LP, Slaviero KA, Clarke SJ. Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response. Br J Cancer. 2002;87:277–280.
  • Harvey RD, Morgan ET. Cancer, inflammation, and therapy: effects on cytochrome p450-mediated drug metabolism and implications for novel immunotherapeutic agents. Clin Pharmacol Ther. 2014;96:449–457.
  • Heimark LD, Gibaldi M, Trager WF, et al. The mechanism of the warfarin-rifampin drug interaction in humans. Clin Pharmacol Ther. 1987;42:388–394.
  • Puisset F, Chatelut E, Dalenc F, et al. Dexamethasone as a probe for docetaxel clearance. Cancer Chemother Pharmacol. 2004;54:265–272.
  • Zamboni WC, Combest AJ, DeLoia JA, et al. Pharmacologic and phenotypic study of docetaxel in patients with ovarian or primary peritoneal cancer. Cancer Chemother Pharmacol. 2011;68:1255–1262.
  • Goh BC, Lee SC, Wang LZ, et al. Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J Clin Oncol. 2002;20:3683–3690.
  • Yamamoto N, Tamura T, Murakami H, et al. Randomized pharmacokinetic and pharmacodynamic study of docetaxel: dosing based on body-surface area compared with individualized dosing based on cytochrome P450 activity estimated using a urinary metabolite of exogenous cortisol. J Clin Oncol. 2005;23:1061–1069.
  • de Graan AJ, Sparreboom A, de Bruijn P, et al. 4β-hydroxycholesterol as an endogenous CYP3A marker in cancer patients treated with taxanes. Br J Clin Pharmacol. 2015;80:560–568.
  • Rouits E, Charasson V, Pétain A, et al. Pharmacokinetic and pharmacogenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer patients. Br J Cancer. 2008;99:1239–1245.
  • Puisset F, Dalenc F, Chatelut E, et al. Dexamethasone as a probe for vinorelbine clearance. Br J Clin Pharmacol. 2005;60:45–53.
  • Wong M, Balleine RL, Blair EY, et al. Predictors of vinorelbine pharmacokinetics and pharmacodynamics in patients with cancer. J Clin Oncol. 2006;24:2448–2455.
  • Gréen H, Skoglund K, Rommel F, et al. CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity. Eur J Clin Pharmacol. 2010;66:383–386.
  • De Wit D, Gelderblom H, Sparreboom A, et al. Midazolam as a phenotyping probe to predict sunitinib exposure in patients with cancer. Cancer Chemother Pharmacol. 2014;73:87–96.
  • Kloth JS, Klümpen HJ, Yu H, et al. Predictive value of CYP3A and ABCB1 phenotyping probes for the pharmacokinetics of sunitinib: the clearsun study. Clin Pharmacokinet. 2014;53:261–269.
  • Li J, Karlsson MO, Brahmer J, et al. CYP3A phenotyping approach to predict systemic exposure to EGFR tyrosine kinase inhibitors. J Natl Cancer Inst. 2006;98:1714–1723.
  • de Jonge H, de Loor H, Verbeke K, et al. Impact of CYP3A5 genotype on tacrolimus versus midazolam clearance in renal transplant recipients: new insights in CYP3A5-mediated drug metabolism. Pharmacogenomics. 2013;14:1467–1480.
  • de Jonge H, de Loor H, Verbeke K, et al. In vivo CYP3A4 activity, CYP3A5 genotype, and hematocrit predict tacrolimus dose requirements and clearance in renal transplant patients. Clin Pharmacol Ther. 2012;92:366–375.
  • Min DI, Ku YM, Vichiendilokkul A, et al. A urine metabolic ratio of dextromethorphan and 3-methoxymorphinan as a probe for CYP3A activity and prediction of cyclosporine clearance in healthy volunteers. Pharmacotherapy. 1999;19:753–759.
  • Villeneuve JP, L’Ecuyer L, De Maeght S, et al. Prediction of cyclosporine clearance in liver transplant recipients by the use of midazolam as a cytochrome P450 3A probe. Clin Pharmacol Ther. 2000;67:242–248.
  • Paine MF, Davis CL, Shen DD, et al. Can oral midazolam predict oral cyclosporine disposition? Eur J Pharm Sci. 2000;12:51–62.
  • DeGorter MK, Tirona RG, Schwarz UI, et al. Clinical and pharmacogenetic predictors of circulating atorvastatin and rosuvastatin concentrations in routine clinical care. Circ Cardiovasc Genet. 2013;6:400–408.
  • Robertson SM, Formentini E, Alfaro RM, et al. Lack of in vivo correlation between indinavir and saquinavir exposure and cytochrome P450 3A phenotype as assessed with oral midazolam as a phenotype probe. Pharmacotherapy. 2006;26:1051–1059.
  • van der Bol JM, Mathijssen RH, Creemers GJ, et al. A CYP3A4 phenotype-based dosing algorithm for individualized treatment of irinotecan. Clin Cancer Res. 2010;16:736–742.
  • Mathijssen RH, de Jong FA, van Schaik RH, et al. Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. J Natl Cancer Inst. 2004;96:1585–1592.
  • Galetin A, Hinton LK, Burt H, et al. Maximal inhibition of intestinal first-pass metabolism as a pragmatic indicator of intestinal contribution to the drug-drug interactions for CYP3A4 cleared drugs. Curr Drug Metab. 2007;8:685–693.
  • Stewart CF, Schuetz EG. Need and potential for predictive tests of hepatic metabolism of anticancer drugs. Clin Cancer Res. 2000;6:3391–3392.
  • Chatelut E, Puisset F. The scientific basis of body surface area-based dosing. Clin Pharmacol Ther. 2014;95:359–361.
  • Shah RR, Smith RL. Addressing phenoconversion: the Achilles’ heel of personalized medicine. Br J Clin Pharmacol. 2015;79:222–240.
  • Hohmann N, Haefeli WE, Mikus G. Use of microdose phenotyping to individualise dosing of patients. Clin Pharmacokinet. 2015;54:893–900.
  • Benet LZ. A holy grail of clinical pharmacology: prediction of drug pharmacokinetics and pharmacodynamics in the individual patient. Clin Pharmacol Ther. 2009;86:133–134.
  • Wurz GT, DeGregorio MW. Activating adaptive cellular mechanisms of resistance following sublethal cytotoxic chemotherapy: implications for diagnostic microdosing. Int J Cancer. 2015;136:1485–1493.
  • Almeida-Paulo GN, Lubomirov R, Alonso-Sanchez NL, et al. Limited sampling strategies for tacrolimus exposure (AUC0–24) prediction after Prograf(®) and Advagraf(®) administration in children and adolescents with liver or kidney transplants. Transpl Int. 2014;27:939–948.

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.