EFFECTS OF PROBENECID ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OFADINAZOLAM IN HUMANS

The effects of probenecid (2 gm) on the pharmacokinetics, pharmacodyna mics, and uricosuric effects of adinazolam and N-desmethyladinazolam w ere assessed after single dose administration of adinazolam mesylate s ustained-release tablets (60 mg) in a randomized, four-way crossover, double-blind study involving 16 healthy male volunteers. Probenecid de creased adinazolam oral clearance, renal N-desmethyladinazolam clearan ce, and the amount of N-desmethyladinazolam excreted in the urine. Pro benecid increased the N-desmethyladinazolam/adinazolam AUC ratio, adin azolam maximum concentration (C-max), N-desmethyladinazolam C-max, and N-desmethyladinoazolam time to reach C-max. Uric acid renal clearance was increased significantly by adinazolam or probenecid administratio n compared with placebo; however, coadministration of adinazolam plus probenecid had no additive effect on uric acid clearance. Psychomotor performance was decreased in the adinazolam plus probenecid treatment compared with the adinazolam treatment. Probenecid potentiated the psy chomotor effects of adinazolam after coadministration of the compounds , predominantly because of alterations in N-desmethyladinazolam pharma cokinetics. Therefore the adinazolam dose may need to be reduced when coadministered with probenecid.