Pharmacokinetics of midazolam and alpha‐hydroxy‐midazolam following rectal and intravenous administration.

Abstract

1. In an open cross‐over trial, plasma concentrations of midazolam were measured in eight healthy male volunteers following administration of 0.3 mg kg‐1 body weight given by the rectal and intravenous routes. 2. Maximum plasma concentrations of 92‐156 ng ml‐1 (mean 118 ng ml‐1) were recorded from 20 to 50 min (mean 31 min) after rectal application. The rectal bioavailability was 40‐65% (mean 52%) and the terminal half‐life was 114‐305 min (mean 161 min). 3. A substantial first‐pass hepatic effect was observed following rectal administration. 4. No systemic or local intolerance was noted. 5. In conclusion, the rectal route of administration provides a rapid and reliable absorption of midazolam. 1988 The British Pharmacological Society