Pharmacokinetics of cloxazolam in man, after single and multiple oral doses
Lavene, D.; Abriol, C.; Guerret, M.; Kiechel, J.R.; Lallemand, A.; Rulliere, R.
Therapie 35(4): 533-543
1980
ISSN/ISBN: 0040-5957 PMID: 6110252 Document Number: 162814
After oral administration of cloxazolam, no measurable amounts of unchanged drug were found in plasma. The assays were performed on chloro-N-demethyl diazepam (CND), which represented the main metabolite. The study was undertaken in 7 subjects after single (2 mg) and multiple oral doses (3 .times. 1 mg daily) for 9 days. CND in plasma samples was determined by electron capture GLC. After .alpha. single dose, CND was found in plasma only after a mean lag time of 0.9 h and reached peak levels (7.79 .+-. 1.6 ng/ml) within 3 h. Then, CND was eliminated with an apparent bi-exponential pattern. Apparent half-life value for the .beta.-phase was 65.9 .+-. 10.8 h. In multiple dosage regimen, the plasma levels were determined 6, 8 and 9 days after initiation of therapy. The steady state was almost reached after 8 days. The mean plasma levels on day 9 were 23.7 .+-. 4.2 ng/ml after the first daily intake and 26.4 .+-. 4.1 ng/ml after the 3rd intake. There was a good correlation with a statistical significance (r = 0.954, P < 0.001) between the observed plasma levels at steady state with the predicted values, based on single dose parameters, which indicates that the pharmacokinetics is linear, nonsaturable, reproducible from administration to administration and that chronic cloxazolam exposure has no apparent effect on its own metabolizing enzymes.