HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Bachmann, K. Articles by Porras, A. G. Search for Related Content PubMed PubMed Citation Articles by Bachmann, K. Articles by Porras, A. G.

An Evaluation of the Dose-Dependent Inhibition of CYP1A2 by Rofecoxib Using Theophylline as a CYP1A2 Probe

From the Department of Pharmacology and Center for Applied Pharmacology (Dr. Bachmann) and the Departments of Mathematics and Pharmacology and Center for Applied Pharmacology (Dr. White), University of Toledo, Toledo, Ohio; Infectious Disease and Center for Applied Pharmacology, St. Vincent Mercy Medical Center, Toledo, Ohio (Dr. Jauregui); and Department of Clinical Pharmacology (Dr. Schwartz), Clinical Biostatistics and Research Data Systems Department (Mr. Larson), and Department of Drug Metabolism (Dr. Porras, Dr. Agrawal, Mr. Mazenko), Merck Research Laboratories, West Point, Pennsylvania.

This study was undertaken to determine whether rofecoxib can interfere with CYP1A2 activity in humans using theophylline as a probe substrate. Single oral doses of theophylline were administered to each of three panels of 12 healthy subjects receiving daily doses of rofecoxib for 7 days to examine the effect of rofecoxib administration on the absorption and disposition of theophylline. Each panel was administered doses of 12.5, 25, or 50 mg of rofecoxib or a matching placebo in a two-way, randomized, crossover fashion and administered a single oral 300-mg dose of theophylline on day 7 of rofecoxib or placebo administration. Plasma concentrations of theophylline were monitored for 48 hours postdose to assess differences in pharmacokinetics. All three commercially marketed doses of rofecoxib were found to slow the clearance of theophylline with no detectable effect on absorption. CL/F values for theophylline were estimated from AUC and by point estimates from the concentrations of drug in plasma at 12 and 24 hours postdose. The point estimates of CL/F were found to be in agreement with those derived from AUC.

Key Words: Rofecoxib • oral • theophylline • drug interaction • oral clearance • point clearance • cyclooxygenase • COX-2 • pharmacokinetics

Address for reprints: Dr. Arturo G. Porras, Merck Research Laboratories, WP26-372, West Point, PA 194886.

This article has been cited by other articles:

				M. J. Karjalainen, P. J. Neuvonen, and J. T. Backman Rofecoxib Is a Potent, Metabolism-Dependent Inhibitor of CYP1A2: Implications for in Vitro Prediction of Drug Interactions Drug Metab. Dispos., December 1, 2006; 34(12): 2091 - 2096. [Abstract] [Full Text] [PDF]

				J. D. Ma, A. N. Nafziger, G. Rhodes, S. Liu, A. M. Gartung, and J. S. Bertino Jr The Effect of Oral Pleconaril on Hepatic Cytochrome P450 3A Activity in Healthy Adults Using Intravenous Midazolam as a Probe J. Clin. Pharmacol., January 1, 2006; 46(1): 103 - 108. [Abstract] [Full Text] [PDF]