title: Pharmacokinetics and protein binding of propofol in patients with cirrhosis.
abstract: The pharmacokinetics and protein binding of propofol were studied in ten patients with cirrhosis and in ten control patients undergoing elective surgery. All patients received 2.5 mg.kg-1 propofol as an intravenous bolus injection for the induction of anesthesia. Whole blood propofol concentrations were measured at intervals up to 12 h, using a high-performance liquid chromatography (HPLC) technique. Propofol protein binding was estimated by equilibrium dialysis 10 min after injection of propofol. Individual propofol profiles for all patients were best described by a three-compartment open mammillary model. Rapid and slow propofol distribution half-times were observed, followed by an elimination phase with a half-time of 4-5 h. Propofol total body clearance was reduced (1.99 +/- 0.68 l.min-1) in the patients with cirrhosis but did not differ significantly from that in the control patients (2.30 +/- 0.61 l.min-1). The apparent volume of distribution at steady state (Vdss) was similar in the two groups. No significant difference in elimination half-life was observed between the two groups. Propofol was extensively bound (mean: 97-98%) to the plasma protein of both cirrhotic and control groups. This study shows that propofol pharmacokinetics and protein binding of propofol following a single intravenous bolus dose were not markedly affected by uncomplicated cirrhosis of the liver.
authors.affiliation: Département d'Anesthésie et de Réanimation Chirurgicale, Hopital Bichat, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Servin
authors.forename: J M
authors.initials: JM
authors.lastname: Desmonts
authors.forename: J P
authors.initials: JP
authors.lastname: Haberer
authors.forename: I D
authors.initials: ID
authors.lastname: Cockshott
authors.forename: G F
authors.initials: GF
authors.lastname: Plummer
authors.forename: R
authors.initials: R
authors.lastname: Farinotti
mesh_terms: D000328:Adult; D000777:Anesthetics / Q000097:blood / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D001835:Body Weight; D005260:Female; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010636:Phenols / Q000097:blood / Q000493:pharmacokinetics*; D015742:Propofol
chemical_list: D000777:Anesthetics; D001798:Blood Proteins; D010636:Phenols; D015742:Propofol