The effects of modifying in vivo cytochrome P450 3A (CYP3A) activity on etoricoxib pharmacokinetics and of etoricoxib administration on CYP3A activity.

Authors

• Nancy G B Agrawal
• Catherine Z Matthews
• Ralph S Mazenko
• Eric J Woolf
• Arturo G Porras
• Xun Chen
• Jutta L Miller
• Nicole Michiels
• Martin Wehling
• Armin Schultz
• Alice B Gottlieb
• Walter K Kraft
• Howard E Greenberg
• Scott A Waldman
• Sean P Curtis
• Keith M Gottesdiener

Publication/Presentation Date

10-1-2004

Abstract

To investigate the influence of modifying in vivo cytochrome P450 3A (CYP3A) activity on the pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, and of etoricoxib administration on CYP3A activity, a 3-part, randomized, crossover study was conducted in 3 panels of healthy volunteers. In part I, 8 subjects were administered a single dose of 60 mg etoricoxib alone and following daily doses of 400 mg ketoconazole, a known strong inhibitor of CYP3A. In part II, 8 different subjects were administered a single dose of 60 mg etoricoxib alone and following daily doses of 600 mg rifampin, a known strong inducer of CYP3A. In parts I and II, plasma samples were collected following each etoricoxib dose and analyzed for etoricoxib. In part III, 8 different subjects were administered 120 mg etoricoxib or placebo once daily for 11 days, and the erythromycin breath test was administered on day 11 of each period. Coadministration of etoricoxib with daily doses of ketoconazole resulted in an average 43% increase in etoricoxib AUC; based on previous studies, this increase would not be expected to have any clinically meaningful effect. In contrast, coadministration of etoricoxib with daily doses of rifampin had a potentially clinically important effect on etoricoxib pharmacokinetics (average 65% decrease in etoricoxib AUC). Etoricoxib had no effect on hepatic CYP3A activity, as assessed by the erythromycin breath test.

Volume

44

Issue

10

First Page

1125

Last Page

1131

ISSN

0091-2700

Published In/Presented At

Agrawal, N. G., Matthews, C. Z., Mazenko, R. S., Woolf, E. J., Porras, A. G., Chen, X., Miller, J. L., Michiels, N., Wehling, M., Schultz, A., Gottlieb, A. B., Kraft, W. K., Greenberg, H. E., Waldman, S. A., Curtis, S. P., & Gottesdiener, K. M. (2004). The effects of modifying in vivo cytochrome P450 3A (CYP3A) activity on etoricoxib pharmacokinetics and of etoricoxib administration on CYP3A activity. Journal of clinical pharmacology, 44(10), 1125–1131. https://doi.org/10.1177/0091270004268129

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

15342613

Department(s)

Administration and Leadership

Document Type

Article