Effects of probenecid on the pharmacokinetics and pharmacodynamics of adinazolam in humans. 1994

P L Golden, and P E Warner, and J C Fleishaker, and R C Jewell, and S Millikin, and J Lyon, and K L Brouwer
Division of Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill 27599-7360.

The effects of probenecid (2 gm) on the pharmacokinetics, pharmacodynamics, and uricosuric effects of adinazolam and N-desmethyladinazolam were assessed after single dose administration of adinazolam mesylate sustained-release tablets (60 mg) in a randomized, four-way crossover, double-blind study involving 16 healthy male volunteers. Probenecid decreased adinazolam oral clearance, renal N-desmethyladinazolam clearance, and the amount of N-desmethyladinazolam excreted in the urine. Probenecid increased the N-desmethyladinazolam/adinazolam AUC ratio, adinazolam maximum concentration (Cmax), N-desmethyladinazolam Cmax, and N-desmethyladinazolam time to reach Cmax. Uric acid renal clearance was increased significantly by adinazolam or probenecid administration 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 psychomotor effects of adinazolam after coadministration of the compounds, predominantly because of alterations in N-desmethyladinazolam pharmacokinetics. Therefore the adinazolam dose may need to be reduced when coadministered with probenecid.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008297 Male Males
D008570 Memory, Short-Term Remembrance of information for a few seconds to hours. Immediate Recall,Memory, Immediate,Working Memory,Memory, Shortterm,Immediate Memories,Immediate Memory,Immediate Recalls,Memories, Immediate,Memories, Short-Term,Memories, Shortterm,Memory, Short Term,Recall, Immediate,Recalls, Immediate,Short-Term Memories,Short-Term Memory,Shortterm Memories,Shortterm Memory,Working Memories
D011339 Probenecid The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Benecid,Benemid,Benuryl,Pro-Cid,Probecid,Probenecid Weimer
D011597 Psychomotor Performance The coordination of a sensory or ideational (cognitive) process and a motor activity. Perceptual Motor Performance,Sensory Motor Performance,Visual Motor Coordination,Coordination, Visual Motor,Coordinations, Visual Motor,Motor Coordination, Visual,Motor Coordinations, Visual,Motor Performance, Perceptual,Motor Performance, Sensory,Motor Performances, Perceptual,Motor Performances, Sensory,Perceptual Motor Performances,Performance, Perceptual Motor,Performance, Psychomotor,Performance, Sensory Motor,Performances, Perceptual Motor,Performances, Psychomotor,Performances, Sensory Motor,Psychomotor Performances,Sensory Motor Performances,Visual Motor Coordinations
D004311 Double-Blind Method A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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