Pharmacokinetics and bioavailability of intravenous and oral chlordesmethyldiazepam in humans.
Six healthy, fasting volunteers were given single doses of chlordesmethyldiazepam by 1 mg i.v., or as drops or tablets. Chlordesmethyldiazepam and its metabolite, lorazepam, in multiple plasma samples and in urine collected for 120 h after each dose were determined by electron-capture GLC. Mean kinetic variables for intravenous chlordesmethyldiazepam were: volume of distribution, 1.71 l.kg-1; elimination half-life, 113 h; total clearance, 0.21 ml.min-1.kg-1; cumulative excretion of lorazepam glucuronide 24.2% of the dose. Following a lag time of 15.5 min (tablets) and 4.2 min (drops), which were significantly different, the absorption of oral chlordesmethyldiazepam was a first order process, with apparent absorption half-life values averaging 1.5 h (tablets) and 1.1 h (drops). Bioavailability was 77% for tablets and 79% for drops.
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D001569:Benzodiazepines; D001682:Biological Availability; D003975:Diazepam / Q000031:analogs & derivatives*; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D003708:Nordazepam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D011897:Random Allocation; D013607:Tablets; D013997:Time Factors
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D013607:Tablets; D001569:Benzodiazepines; D003708:Nordazepam; C013434:chlordesmethyldiazepam; D003975:Diazepam