Pharmacokinetics and protein binding of propofol in patients with cirrhosis.
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.
Servin
F
F
Département d'Anesthésie et de Réanimation Chirurgicale, Hopital Bichat, Paris, France.
Desmonts
J M
JM
Haberer
J P
JP
Cockshott
I D
ID
Plummer
G F
GF
Farinotti
R
R
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
D000777:Anesthetics; D001798:Blood Proteins; D010636:Phenols; D015742:Propofol