Interaction of oxaprozin with acetaminophen, cimetidine, and ranitidine.
Twelve healthy male volunteers participated in a single-dose four-way crossover study to evaluate potential drug interactions with oxaprozin, a nonsteroidal antiinflammatory agent of the propionic class. The four modes of administration were: a. oxaprozin, 1200 mg alone; b. oxaprozin during concurrent acetaminophen, 500 mg 4 times daily; c. oxaprozin with cimetidine, 300 mg 4 times daily; d. oxaprozin with ranitidine, 150 mg every 12 hours. Acetaminophen, cimetidine, or ranitidine were begun 24 hours prior to oxaprozin dosage and continued for the 10-day duration of each trial. No significant differences existed among the four treatment conditions in peak plasma oxaprozin concentration (86 micrograms/ml), volume of distribution (0.23 l/kg), time of peak concentration (3.7 h after dosage), or elimination half-life (54 h). Oxaprozin oral clearance was significantly lower (by 20%) during both the cimetidine and ranitidine trials versus control (0.047 vs 0.047 vs 0.059 ml/min/kg), but clearance during acetaminophen was not significantly different from control. Thus acetaminophen, cimetidine or ranitidine has only a small influence on the pharmacokinetics of a single oral dose of oxaprozin. The reduction in oxaprozin clearance due to cimetidine or ranitidine is statistically significant but small in magnitude.
D000082:Acetaminophen / Q000494:pharmacology*; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism*; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D000077431:Oxaprozin; D011422:Propionates / Q000008:administration & dosage / Q000378:metabolism*; D011899:Ranitidine / Q000494:pharmacology*; D012044:Regression Analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; D000082:Acetaminophen; D002927:Cimetidine; D011899:Ranitidine; D000077431:Oxaprozin