Midazolam kinetics.
The effect-kinetics of the new benzodiazepine midazolam was evaluated in six subjects after single oral (7.5 and 15 mg) and intravenous (0.075 mg/kg) doses and infusion programs. The drug is bound to plasma proteins by 94%, and less than 0.5% is excreted unchanged in urine. Hepatic elimination is rapid: t1/2 beta is 2.4 +/- 0.8 hr (mean +/- S.D) 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 = 0.23 +/- 0.37 hr) 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 analogue scales.
D000284:Administration, Oral; D000328:Adult; D014151:Anti-Anxiety Agents / Q000378:metabolism* / Q000494:pharmacology; D001569:Benzodiazepines / Q000378:metabolism* / Q000494:pharmacology; D001682:Biological Availability; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008874:Midazolam
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D008874:Midazolam