CYP3A probes can quantitatively predict the in vivo kinetics of other CYP3A substrates and can accurately assess CYP3A induction and inhibition

Molecular Interventions

Volumn 5, Issue 3, 2005, Pages 151-153

  Kharasch, Evan D ^a,b   Thummel, Kenneth E ^a,c   Watkins, Paul B ^a,d,e,f  

^a Department of Anesthesiology ^*  (United States)

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

^c UNIVERSITY OF WASHINGTON   (United States)

^d UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^e METABOLIC SOLUTIONS INC   (United States)

^f UNIVERSITY OF NORTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 3A;

ACCURACY; DRUG CLEARANCE; ENZYME ACTIVITY; ENZYME INDUCTION; ENZYME INHIBITION; ENZYME KINETICS; ENZYME SUBSTRATE; IN VIVO STUDY; MOLECULAR PROBE; PREDICTION; QUANTITATIVE ANALYSIS; SHORT SURVEY;

ALFENTANIL; ANALGESICS, OPIOID; ANESTHETICS, INTRAVENOUS; CYTOCHROME P-450 CYP3A; ENZYME INDUCTION; HUMANS; KINETICS; MIDAZOLAM; MOLECULAR PROBES; SAMPLE SIZE; SUBSTRATE SPECIFICITY;

EID: 22544435261     PISSN: 15340384     EISSN: None     Source Type: Journal    
DOI: 10.1124/mi.5.3.3     Document Type: Short Survey

References (21)

1. Watkins, P.B. Noninvasive tests of CYP3A enzymes. Pharmacogenetics 4, 171-184 (1994).
2. Guidance for industry: In vivo drug metabolism/drug interaction studies -Study design, data analysis, and recommendations for dosing and labeling. US FDA, Center for Drug Evaluation and Research (1999).
3. Tucker, G.T., Houston, J.B., and Huang, S.-M. Optimizing drug development: strategies to assess drug metabolism/transporter interaction potential-toward a consensus. Clin. Pharmacol. Ther. 70, 103-114 (2001).
4. Huang, S.-M. Issues and challenges in the evaluation and labeling of drug interaction potentials of new molecular entities. CDER Advisory Committee for Pharmaceutical Sciences Clinical Pharmacology Subcommittee Meeting, April 23, 2003 (http://www.fda.gov/ohrms/dockets/ ac/03/slides/3947S2_02_Huang.ppt)
5. Bjornsson, T.D., Callaghan, J.T., Einolf, H.J. et al. The conduct of in vitro and in vivo drug-drug interaction studies: a pharmaceutical research and manufacturers of America (PhRMA) perspective. Drug Metab. Dispos. 31, 815-832 (2003). Describes recommendations to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies for drug development and to achieve consistency in the quality and predictability for drug-drug interaction studies.
6. Dees, E.C. and Watkins, P.B. Role of cytochrome P450 phenotyping in cancer treatment. J Clin Oncol 23, 1053-1055 (2005). This Editorial addresses interindividual variability in the therapeutic response and toxicity of cancer treatment. It accompanied an article reporting the first prospective study which compared individualized dosing of chemotherapy based on CYP3A phenotyping to standard dosing, demonstrating that individualized dosing based on CYP3A4 phenotype can reduce interpatient variability.
7. Benet, L.Z. There are no useful CYP3A probes that quantitatively predict the in vivo kinetics of other CYP3A substrates and no expectation that one will be found. Mol. Interv. 5, 79-83 (2005).
8. Masica, A.L., Mayo, G., and Wilkinson, G.R. In vivo comparisons of constitutive cytochrome P450 3A activity assessed by alprazolam, triazolam, and midazolam. Clin. Pharmacol. Ther. 76, 341-349 (2004).
9. Kharasch, E.D., Russell, M., Mautz, D., Thummel, K.E., Kunze, K.L., Bowdle, T.A., and Cox, K. The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions. Anesthesiology 87, 36-50 (1997).
10. Kharasch, E.D., Walker, A., Hoffer, C., and Sheffels, P. Intravenous and oral alfentanil as in vivo probes for hepatic and first-pass CYP3A activity. Noninvasive assessment using pupillary miosis. Clin Pharmacol. Ther. 76, 452-466 (2004). Demonstrates the highly significant relationships between the CYP3A substrates alfentanil and midazolam, with respect to systemic clearances, oral clearances and hepatic extraction.
11. Thummel, K.E., O'Shea, D., Paine, M.F., Shen, D.D., Kunze, K.L., Perkins, J.D., and Wilkinson, G.R. Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin. Pharmacol. Ther. 59, 491-502 (1996).
12. Paine, M.F., Khalighi, M., Fisher, J.M., Shen, D.D., Kunze, K.L., Marsh, C.L., Perkins, J.D., and Thummel, K.E. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J. Pharmacol. Exp. Ther. 283, 1552-1562 (1997).
13. Gorski, J.C., Jones, D.R., Haehner-Daniels, B.D., Hamman, M.A., O'Mara, E.M., Jr., and Hall, S.D. The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin. Clin. Pharmacol. Ther. 64, 133-143 (1998).
14. Kharasch, E., Hoffer, C., Walker, A., and Sheffels, P. Alfentanil pharmacogenetics: The role of polymorphic cytochrome P4503A5 (CYP3A5) expression in alfentanil disposition. Proc. Assoc. Univ. Anesthesiologists, in press (2005).
15. Kharasch, E.D., Jubert, C., Senn, T., Bowdle, T.A., and Thummel, K.T. Intraindividual variability in male hepatic CYP3A4 activity assessed by alfentanil and midazolam clearance. J. Clin. Pharmacol. 39, 664-669 (1999).
16. Kharasch, E.D., Walker, A., Hoffer, C., and Sheffels, P. Evaluation of first-pass cytochrome P4503A (CYP3A) and P-glycoprotein activities using alfentanil and fexofenadine in combination. J. Clin. Pharmacol. 45, 79-88 (2005).
17. Hamman, M.A., Bruce, M.A., Haehner-Daniels, B.D., and Hall, S.D. The effect of rifampin administration on the disposition of fexofenadine. Clin. Pharmacol. Ther. 69, 114-121 (2001).
18. Kim, R.B., Leake, B.F., Choo, E.F. et al. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin. Pharmacol. Ther. 70, 189-199 (2001).
19. Drescher, S., Schaeffeler, E., Hitzl, M., Hofmann, U., Schwab, M., Brinkmann, U., Eichelbaum, M., and Fromm, M.F. MDR1 gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine. Br. J. Clin. Pharmacol. 53, 526-534 (2002).
20. 14C]erythromycin breath and urine test. Am. J. Physiol. Gastrointest. Liver Physiol. 285, G470-G482 (2003).
21. Mathijssen, R.H., de Jong, F.A., van Schaik, R.H. et al. Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. J Natl Cancer Inst 96, 1585-1592 (2004). Showed that CYP3A4 phenotype, as assessed by midazolam clearance, was significantly associated with the clearance of irinotecan, and suggested that evaluation of CYP3A4 activity may assist with optimization of irinotecan chemotherapy.