Influence of repeated administration of cimetidine on the pharmacokinetics and pharmacodynamics of adinazolam in healthy subjects.
Adinazolam is a new triazolobenzodiazepine bearing an alkyl-amino side chain. A cross-over double-blind placebo controlled study was carried out in 12 healthy volunteers, in order to check the possible interaction between cimetidine and adinazolam after repeated co-administration. Cimetidine or placebo were given during 17 days. Beginning on Day 8 of each treatment, adinazolam was given in the increasing doses following sequence of doses for 3 days: 10 mg b.i.d., 20 mg b.i.d. and 20 mg t.i.d. A pharmacokinetic and pharmacodynamic study was performed on the third day at each dose. A wash-out of three weeks was included between the two treatments. Cimetidine increased significantly the AUC values of both adinazolam and N-desmethyladinazolam, reduced the oral clearance of adinazolam, and prolonged adinazolam's half-life. The digit symbol substitution test was significantly affected at each dose level while the manual dexterity was marginally impaired by adinazolam plus cimetidine. Saftee-up interview and Clyde mood scale indicated an increased sedation under adinazolam plus cimetidine in four subjects.
Hulhoven
R
R
Laboratoire de Pharmacothérapie, Université Catholique de Louvain, Bruxelles, Belgium.
Desager
J P
JP
Cox
S
S
Harvengt
C
C
D000328:Adult; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D001569:Benzodiazepines / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D001711:Biotransformation; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D004644:Emotions / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D011600:Psychopharmacology
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D001569:Benzodiazepines; D002927:Cimetidine; C039668:adinazolam