Midazolam kinetics

Abstract

The effect-kinetics of the new benzodiazepine midazolam [used for i.v. anesthesia induction] was evaluated in 6 subjects [human] after single oral (7.5 and 15 mg) and i.v. (0.075 mg/kg) doses and infusion programs. The drug is bound to plasma proteins by 94%, and < 0.5% is excreted unchanged in urine. Hepatic elimination is rapid: t1/2.beta. [half-life] is 2.4 .+-. 0.8 h (.hivin.x [mean] .+-. SD) and total body clearance is 283 .+-. 43 ml/min (plasma) or 502 .+-. 105 ml/min (blood). This substantial first-pass effect leads to bioavailability of only 44%, despite very rapid absorption (t1/2abs [absorption half-life] = 0.23 .+-. 0.37 h) after oral dosing. There is good intraindividual linear correlations (r between 0.68 and 0.97) between plasma levels and dynamic effects, as assessed by the d2 letter cancellation test and a sedation index formed from visual analog scales.