Effect of probenecid on isofezolac kinetics.

The interaction between isofezolac and probenecid has been studied with the aid of a specific HPLC assay for isofezolac in plasma and urine. 8 healthy adult volunteers received a single 40 mg oral dose of isofezolac before and after 3 days of loading with 0.5 probenecid t.i.d. There was an increase in the maximum plasma isofezolac concentration from 2.44 to 3.38 micrograms X ml-1 when probenecid was given. The AUC of isofezolac in plasma increased from 6.73 to 11.28 micrograms X h X ml-1. After the last dose in a 7 day treatment with 40 mg isofezolac t.i.d., there was an increase in the maximum plasma isofezolac level from 2.84 to 4.96 micrograms X ml-1 when probenecid was given. The rate of absorption of isofezolac was not affected. An increase in the AUC of isofezolac in plasma was observed from 11.74 to 26.34 micrograms X h X ml-1. The major effect of probenecid on isofezolac metabolism was a 50% reduction in total isofezolac (free + conjugates) excreted inurine. Because of this interaction, patients given isofezolac combined with probenecid will have a higher steady-state plasma level of isofezolac than when probenecid is not administered.