Abstract:
: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 infinity 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.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Bachmann K,White D,Jauregui L,Schwartz JI,Agrawal NG,Mazenko R,Larson PJ,Porras AGdoi
10.1177/0091270003257454subject
Has Abstractpub_date
2003-10-01 00:00:00pages
1082-90issue
10eissn
0091-2700issn
1552-4604pii
43/10/1082journal_volume
43pub_type
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