[Pharmacokinetics of midazolam in man (author's transl)]

Plasma concentrations of midazolam (Ro 21-3981/001) were studied in six gynaecological patients following a 12.5 mg intravenous bolus injection of the drug for induction of anaesthesia. The plasma decay curves were found to be biphasic. Therefore the data were interpreted according to an open two compartment model. The fast distribution phase (alpha-phase) lasted about 30 to 45 min with a mean halflife of about 8-9 min. The half-life of the slow redistribution and elimination phase (beta-phase) amounted to a mean of about 150 min. The apparent volume of distribution of the cental compartment (V1) was calculated as 24.11 and the volume of distribution at steady state as 84.21 (Vd, ss). The volume of distribution in the beta-phase (Vd beta) ranged from 71.5 to 129.51 with a mean of 104.21. The total plasma clearance varied from 380 to 527 ml/min with a mean of 472 ml/min. It is suggested that the pharmacokinetic behavior is due to water-solubility and plasma protein binding of this new benzodiazepine.