Pharmacokinetics, safety, and tolerability of BAY 12-9566 and nonsteroidalanti-inflammatory agents (naproxen, ibuprofen) during coadministration in patients with osteoarthritis

The pharmacokinetic interactions between BAY 12-9566 and two nonsteroidal a nti-inflammatory drugs (NSAIDs), naproxen and ibuprofen, were investigated in osteoarthritis (OA) patients. The study comprised six groups: two NSAID groups with three levels of treatment (BAY 12-9566 400 mg, BAY 12-9566 100 mg, and placebo). Plasma pharmacokinetic parameters (AUC(0-tau), C-max, and t(max)) were determined for each treatment group following 5 days of NSAID administration, 14 days of BAY 12-9566 administration, and 14 days of conc urrent NSAID and BAY 12-9566 administration. For most conditions, the total plasma drug concentrations of both NSAID and BAY 12-9566 were diminished b y coadministration; total plasma BAY 12-9566 eras not affected by ibuprofen treatment. Importantly, the free drug concentrations were largely unaffect ed by coadministration. Most side effects were mild or moderate in intensit y, and all events, with the exception of headache, were reported in both NS AID groups and in both placebo and BAY 12-9566 groups. Journal of Clinical Pharmacology, 2001;41:330-339 (C) 2001 the American College of Clinical Pha rmacology.