PHARMACOKINETICS OF GENTAMICIN IN RABBITS PRETREATED WITH NONSTEROIDAL ANTIINFLAMMATORY DRUGS - AN INTERACTION STUDY

Interaction between nonsteroidal anti-inflammatory drugs (NSAIDs) and other drugs occurs relatively frequently because of the wide use of NS AIDs. Such interactions with drugs of narrow therapeutic index used in serious disease states may lead to toxicity. Gentamicin toxicity is b ased on its concentration in serum, and any alteration in pharmacokine tic parameters may lead to gentamicin accumulation in the body and sub sequently to severe nephrotoxicity and ototoxicity. To test this hypot hesis, the effect of pretreatment with NSAIDs on gentamicin pharmacoki netics was examined in rabbit. Gentamicin sulfate (5 mg/kg) was admini stered to rabbits pretreated with aspirin (300 mg/kg), ketorolac trome thamine (3 mg/kg), ibuprofen (20 mg/ kg), and piroxicam (2 mg/kg) twic e a day for 1 week. The pretreatment with NSAIDs had significant effec ts on the body clearance and maximum concentration. Aspirin, piroxicam and ketorolac tromethamine pretreatment had significant effects on th e area under the curve of gentamicin versus time. Aspirin and ketorola c tromethamine pretreatment had significant effects on the half-life o f gentamicin. Aspirin had a significant effect on the volume of distri bution of gentamicin. These results suggest that pretreatment with NSA IDs alters the pharmacokinetics of gentamicin and leads to accumulatio n inside the body, which could result in toxicity.