Adinazolam pharmacokinetics and behavioral effects following administration of 20-60 mg oral doses of its mesylate salt in healthy volunteers.
The pharmacokinetics and pharmacodynamics of adinazolam were studied in 15 normal, healthy, non-obese volunteers. Placebo capsules and capsules containing 20, 40, and 60 mg adinazolam mesylate were administered as single oral doses in a randomized, 4-way crossover design. Plasma concentrations of adinazolam and mono-N-desmethyladinazolam (NDMAD) were determined by HPLC. Psychomotor performance and memory tests were performed and the degree of sedation assessed at designated times following drug administration. Adinazolam and NDMAD pharmacokinetics were linear throughout the dosage range studied. The ratio of NDMAD to adinazolam area under the curve was approximately 4:1. Dose-related decrements in psychomotor performance and memory were observed up to 8 h after dosing (P less than 0.025 in all cases). Psychomotor performance decrements correlated more closely with NDMAD plasma concentrations than with adinazolam concentrations. These results suggest that NDMAD is responsible for a significant degree of the sedative and psychomotor effects observed after the administration of adinazolam.
Fleishaker
J C
JC
Clinical Pharmacokinetics Unit, Upjohn Company, Kalamazoo, MI 49001.
Phillips
J P
JP
D000284:Administration, Oral; D000328:Adult; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; C039668:adinazolam; C050132:mono-N-demethyladinazolam