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

J Clin Pharmacol. 2001 Mar;41(3):330-9. doi: 10.1177/00912700122010032.

Abstract

The pharmacokinetic interactions between BAY 12-9566 and two nonsteroidal anti-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), Cmax, and tmax) were determined for each treatment group following 5 days of NSAID administration, 14 days of BAY 12-9566 administration, and 14 days of concurrent NSAID and BAY 12-9566 administration. For most conditions, the total plasma drug concentrations of both NSAID and BAY 12-9566 were diminished by coadministration; total plasma BAY 12-9566 was not affected by ibuprofen treatment. Importantly, the free drug concentrations were largely unaffected by coadministration. Most side effects were mild or moderate in intensity, and all events, with the exception of headache, were reported in both NSAID groups and in both placebo and BAY 12-9566 groups.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / blood
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use
  • Area Under Curve
  • Biphenyl Compounds
  • Chromatography, High Pressure Liquid
  • Double-Blind Method
  • Drug Interactions / physiology
  • Drug Therapy, Combination
  • Female
  • Humans
  • Ibuprofen / blood
  • Ibuprofen / pharmacokinetics*
  • Ibuprofen / therapeutic use
  • Male
  • Metalloendopeptidases / antagonists & inhibitors
  • Middle Aged
  • Naproxen / blood
  • Naproxen / pharmacokinetics*
  • Naproxen / therapeutic use
  • Organic Chemicals*
  • Osteoarthritis / drug therapy*
  • Phenylbutyrates

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Biphenyl Compounds
  • Organic Chemicals
  • Phenylbutyrates
  • Naproxen
  • Bay 12-9566
  • Metalloendopeptidases
  • Ibuprofen