Pharmacokinetics of gentamicin in rabbits pretreated with nonsteroidal anti-inflammatory drugs: an interaction study.

Abstract:

:Interaction between nonsteroidal anti-inflammatory drugs (NSAIDs) and other drugs occurs relatively frequently because of the wide use of NSAIDs. Such interactions with drugs of narrow therapeutic index used in serious disease states may lead to toxicity. Gentamicin toxicity is based on its concentration in serum, and any alteration in pharmacokinetic parameters may lead to gentamicin accumulation in the body and subsequently to severe nephrotoxicity and ototoxicity. To test this hypothesis, the effect of pretreatment with NSAIDs on gentamicin pharmacokinetics was examined in rabbit. Gentamicin sulfate (5 mg/kg) was administered to rabbits pretreated with aspirin (300 mg/kg), ketorolac tromethamine (3 mg/kg), ibuprofen (20 mg/kg), and piroxicam (2 mg/kg) twice a day for 1 week. The pretreatment with NSAIDs had significant effects on the body clearance and maximum concentration. Aspirin, piroxicam and ketorolac tromethamine pretreatment had significant effects on the area under the curve of gentamicin versus time. Aspirin and ketorolac tromethamine pretreatment had significant effects on the half-life of gentamicin. Aspirin had a significant effect on the volume of distribution of gentamicin. These results suggest that pretreatment with NSAIDs alters the pharmacokinetics of gentamicin and leads to accumulation inside the body, which could result in toxicity.

journal_name

J Pharm Sci

authors

Shivprakash,Gandhi TP,Patel RB,Sheikh MA,Jhala A,Santani DD

doi

10.1002/jps.2600830419

subject

Has Abstract

pub_date

1994-04-01 00:00:00

pages

542-4

issue

4

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)49431-6

journal_volume

83

pub_type

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