Preliminary study of the pharmacokinetics of desmethyldiazepam administered as drops or tablets

Desmethyldiazepam (Vegesan) was administered in the form of 5-mg and 10-mg tablets and of 10-mg drops to 4 male and 4 female young healthy volunteers. The plasma levels of desmethyldiazepam were measured over 168 h. The time courses could be fitted to the one- or to the two-compartment model. The mean half-lives of elimination came to 75.3 +/- 32.0 (SD) h (5-mg tablets), 66.5 +/- 21.0 (SD) h (10-mg tablets) and 78.4 +/- 33.2 (SD) h (10-mg drops). The bioavailability of desmethyldiazepam from tablets and from drops was practically the same. The bioavailability appeared to be independent of dose in this range. A significantly higher total plasma clearance was calculated for the male than for the female volunteers after all three dosage forms (p less than 0.05). The total plasma clearance lay between 4.8 and 13.0 ml/min for the female and 12.4 and 24.3 ml/min for the male volunteers. Ingestion of the contraceptive pill is suggested as a possible cause of the sex differences.