Extra-hepatic metabolism of midazolam.
Six patients received 10 mg of midazolam intravenously during the anhepatic period of liver transplantation. Arterial blood was sampled during this time and for a similar period following revascularisation. The plasma was analysed using gas chromatography and electron capture detection (GC-ECD) for midazolam alpha-hydroxymidazolam and alpha-hydroxymidazolam glucuronide. Five of the six patients had small but significant concentrations of metabolites detected during the anhepatic period, demonstrating the presence of extra-hepatic sites of metabolism for this drug. The remaining patient had plasma concentrations of metabolites below the lower limit of detection (2 micrograms l-1). This may represent a pharmacogenetic abnormality or a temporary failure of midazolam metabolism secondary to the patients illness affecting the extra-hepatic sites of metabolism.
Park
G R
GR
Department of Anaesthesia, Addenbrooke's Hospital, Cambridge.
Manara
A R
AR
Dawling
S
S
D000328:Adult; D005260:Female; D006801:Humans; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D008874:Midazolam / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D008875:Middle Aged
C040081:1-hydroxymethylmidazolam; D008874:Midazolam