title: Pharmacokinetics of midazolam in anaesthetized cirrhotic patients.
abstract: The pharmacokinetics of midazolam were compared in cirrhotic patients (n = 10) and control patients (n = 9), during general anaesthesia. Total plasma clearance was 637 +/- 223 ml min-1 (mean +/- SD) in control patients and 402 +/- 170 ml min-1 in cirrhotic patients (P less than 0.05). The total volume of distribution was similar. Elimination half-life was 135 +/- 40 min in controls and 168 +/- 30 min in cirrhosis (P less than 0.05). Protein binding was evaluated by equilibrium dialysis in both groups at two concentrations of midazolam: 20 and 500 micrograms litre-1. No saturation occurred, but the free fraction was 4.9 +/- 1.7% in cirrhotic patients, compared with 1.9 +/- 0.6% in controls (P less than 0.01). Despite its mainly hepatic elimination, midazolam disposition appears to be only slightly impaired in cirrhotic patients.
authors.affiliation: Département d'Anesthésiologie, Hôpital Bichat, Paris, France.
authors.forename: J H
authors.initials: JH
authors.lastname: Trouvin
authors.forename: R
authors.initials: R
authors.lastname: Farinotti
authors.forename: J P
authors.initials: JP
authors.lastname: Haberer
authors.forename: F
authors.initials: F
authors.lastname: Servin
authors.forename: M
authors.initials: M
authors.lastname: Chauvin
authors.forename: P
authors.initials: P
authors.lastname: Duvaldestin
mesh_terms: D000328:Adult; D000368:Aged; D000768:Anesthesia, General; D005260:Female; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D012709:Serum Albumin; D008874:Midazolam