[Pharmacokinetics of midazolam after i.v. administration (author's transl)]

Abstract

8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a] [1,4] benzodiazepine (midazolam, Ro 21-3981, Dormicum) is a special type of benzodiazepine. Its salts are water-soluble and also stable in an aqueous solution. Following i.v. injection of the substance, the human body eliminates midazolam almost entirely by means of biotransformation. Following rapid i.v. injection of midazolam into 8 normal volunteers, the plasma concentration of the substance decreases to approximately 10% within 1 h owing to a rapid rate of distribution. The biological half-life in the terminal phase (beta) ranges between 1 1/2 and 2 1/2 h. In view of the non-dose-dependent clearance and the various phases of distribution, the pharmacokinetic behaviour of the drug can be described by means of a linear three-compartmental model. The portion of drug extracted by the liver ranges between 40 and 50%, which implies a liver first-pass effect of approximately 50% after oral administration. The total plasma clearance is 300-350 ml/min. The absorption rate after i.m. injection is extremely rapid, with complete absorption taking place.