Accurate prediction of dose-dependent CYP3A4 inhibition by itraconazole and its metabolites from in vitro inhibition data

Clinical Pharmacology and Therapeutics

Volumn 88, Issue 4, 2010, Pages 499-505

  Templeton, I ^a   Peng, C C ^a   Thummel, K E ^a   Davis, C ^b   Kunze, K L ^a   Isoherranen, N ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 3A4; DRUG METABOLITE; HYDROXYITRACONAZOLE; ITRACONAZOLE; KETO ITRACONAZOLE; MIDAZOLAM; N DESALKYLITRACONAZOLE; UNCLASSIFIED DRUG; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450 3A INHIBITOR; ENZYME INHIBITOR;

ADULT; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG ANTAGONISM; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; IC 50; IN VITRO STUDY; MALE; NAUSEA AND VOMITING; NORMAL HUMAN; PRIORITY JOURNAL; AREA UNDER THE CURVE; CLINICAL TRIAL; DRUG INTERACTION; IC50; METABOLIC CLEARANCE RATE; YOUNG ADULT;

ADULT; AREA UNDER CURVE; CYTOCHROME P-450 CYP3A; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; ENZYME INHIBITORS; FEMALE; HUMANS; INHIBITORY CONCENTRATION 50; ITRACONAZOLE; MALE; METABOLIC CLEARANCE RATE; MIDAZOLAM; YOUNG ADULT; CYTOCHROME P-450 CYP3A INHIBITORS; IN VITRO TECHNIQUES;

EID: 77957019850     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/clpt.2010.119     Document Type: Article

References (17)

1. Isoherranen, N., Hachad, H., Yeung, C.K. & Levy, R.H. Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database. Chem. Res. Toxicol. 22, 294-298 (2009).
2. Fujioka, Y., Yeung, C.K., Hachad, H., Levy, R.H. & Isoherranen, N. Analysis of the contribution of circulating metabolites to inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database. Drug Metab Rev 41 (suppl. 3), 69 (2009).
3. Isoherranen, N., Kunze, K.L., Allen, K.E., Nelson, W.L. & Thummel, K.E. Role of itraconazole metabolites in CYP3A4 inhibition. Drug Metab. Dispos. 32, 1121-1131 (2004).
4. Stevens, J.C. & Wrighton, S.A. Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P450. J. Pharmacol. Exp. Ther. 266, 964-971 (1993).
5. Reese, M.J., Wurm, R.M., Muir, K.T., Generaux, G.T., St John-Williams, L. & McConn, D.J. An in vitro mechanistic study to elucidate the desipramine/ bupropion clinical drug-drug interaction. Drug Metab. Dispos. 36, 1198-1201 (2008).
6. Preskorn, S.H., Alderman, J., Chung, M., Harrison, W., Messig, M. & Harris, S. Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. J. Clin. Psychopharmacol. 14, 90-98 (1994).
7. Sauer, J.M. et al. Atomoxetine hydrochloride: clinical drug-drug interaction prediction and outcome. J. Pharmacol. Exp. Ther. 308, 410-418 (2004).
8. T empleton, I.E. et al. Contribution of itraconazole metabolites to inhibition of CYP3A4 in vivo. Clin. Pharmacol. Ther. 83, 77-85 (2008).
9. Olkkola, K.T., Ahonen, J. & Neuvonen, P.J. The effect of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth Analg (Baltimore) 82, 511-516 (1996).
10. Olkkola, K.T., Brunetto, A.V. & Mattila, M.J. Pharmacokinetics of oxicam nonsteroidal anti-inflammatory agents. Clin. Pharmacokinet. 26, 107-120 (1994).
11. Ahonen, J., Olkkola, K.T. & Neuvonen, P.J. Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers. Br. J. Clin. Pharmacol. 40, 270-272 (1995).
12. Neuvonen, P.J., Varhe, A. & Olkkola, K.T. The effect of ingestion time interval on the interaction between itraconazole and triazolam. Clin. Pharmacol. Ther. 60, 326-331 (1996).
13. Backman, J.T., Kivistö, K.T., Olkkola, K.T. & Neuvonen, P.J. 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 (1998).
14. Levy, R.H., Hachad, H., Yao, C. & Ragueneau-Majlessi, I. Relationship between extent of inhibition and inhibitor dose: literature evaluation based on the metabolism and transport drug interaction database. Curr. Drug Metab. 4, 371-380 (2003).
15. Yao, C., Kunze, K.L., Trager, W.F., Kharasch, E.D. & Levy, R.H. Comparison of in vitro and in vivo inhibition potencies of fluvoxamine toward CYP2C19. Drug Metab. Dispos. 31, 565-571 (2003).
16. Obach, R.S., Walsky, R.L., Venkatakrishnan, K., Gaman, E.A., Houston, J.B. & Tremaine, L.M. The utility of in vitro cytochrome P450 inhibition data in the prediction of drug-drug interactions. J. Pharmacol. Exp. Ther. 316, 336-348 (2006).
17. Paine, M.F. et al. First-pass metabolism of midazolam by the human intestine. Clin. Pharmacol. Ther. 60, 14-24 (1996).