Pharmacokinetics and bioavailability of midazolam in man

The pharmacokinetic behaviour and the bioavailability of midazolam were investigated in six volunteers after intravenous (0.15 mg/kg) and oral administration (10, 20 and 40 mg). Following rapid intravenous injection of midazolam, the plasma concentration of the substance decreased to approximately 10% within 2 h owing to a rapid rate of distribution. A two compartment model adequately described the kinetics of midazolam in plasma. The following average values were found: elimination half-life, 2.3 h; total clearance, 323 ml/min, and apparent volume of distribution at steady-state (VSS), 50.21. After oral administration, the drug is rapidly absorbed. Maximum plasma levels are reached within 30 min and the drug is rapidly eliminated from plasma with practically the same half-life as determined after i.v. administration. The bioavailability after the ingestion of 10, 20 and 40 mg midazolam in the form of tablets ranged from 31 to 72%, due to the high liver extraction quota of midazolam.