Desmethyldiazepam kinetics after intravenous, intramuscular, and oral administration of clorazepate dipotassium

Abstract

The pharmacokinetics and bioavailability of desmethyldiazepam (DMDZ), formed from its precursor clorazepate (CZP) dipotassium, were assessed in a series of 17 healthy volunteers aged 21--66 years. After a single 20-mg intravenous dose of CZP, mean kinetic variables for DMDZ were: volume of distribution, 1.24 l/kg; elimination half-life, 65 h; total clearance, 0.24 ml/min/kg. Among males, DMDZ half-life tended to be prolonged and clearance reduced with age, but this was not true for females. After oral administration of 20 mg CZP, appearance of DMDZ in the circulation was rapid; the mean peak plasma level was 356 ng/ml, reached an average of 0.9 h after dosage. Based on comparison with IV dosage, systemic availability of DMDZ was complete (100% absorption). Ten of the subjects also received a single 20-mg intramuscular dose of CZP. Mean peak DMDZ levels were 290 ng/ml, reaching an average of 2.7 h after dosage. Systemic availability of DMDZ was complete. Elimination half-life of DMDZ for a given individual was highly replicable from trial to trial regardless of the route of CZP administration.