Pharmacokinetics of midazolam and alpha-hydroxy-midazolam following rectal and intravenous administration.
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.
Clausen
T G
TG
Department of Anaesthesia, Bispebjerg Hospital, Copenhagen, Denmark.
Wolff
J
J
Hansen
P B
PB
Larsen
F
F
Rasmussen
S N
SN
Dixon
J S
JS
Crevoisier
C
C
D000285:Administration, Rectal; D000328:Adult; D001682:Biological Availability; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
C040081:1-hydroxymethylmidazolam; D008874:Midazolam