EFFECTS OF DIFFERENT HEPATIC PATHOLOGIES ON DISPOSITION OF ALFENTANIL IN ANAESTHETIZED PATIENTS

We have studied the influence of different hepatic pathologieson the disposition of alfentanil in 23 unpremedicated patients(six healthy control subjects, six patients with liver dysfunctionof alcoholic aetiology and 11 patients with non-alcohol relatedliver disease). All patients received a bolus of alfentanil500 fig i.v. as supplement to 67% nitrous oxide and isofluranein oxygen anaesthesia. Plasma drug concentrations were measuredin venous blood samples at intervals up to 24 h by radio-immunoassayand protein binding was determined by equilibrium dialysis.Kinetic estimates were determined using non-compartmental analysis.Patients with non-alcoholic liver disease had lesser plasmaclearance (114.8 (range 66.8–213.5) ml min^–1) thanthe alcoholic group (158.8 (100.0–220.7) ml min^–1)or controls (187.4 (125.2–269.5) ml min^–1). In allthree groups, there was considerable intersubject variability,with a bimodal distribution in the non-alcoholic group. Thisgroup also had a smaller apparent volume of distribution atsteady state. Mean residence time was prolonged in the alcoholicgroup compared with controls (284.9 (217.8–362.2) minvs 226.8 (201.2–250) min). Protein binding was decreasedin the alcoholic group compared with controls (84.9 (SD 4.2)%vs 89.3 (2.1)%); this was attributable to a lesser plasma a,-acidglycoprotein concentration (0.55 (0.18) g litre^–1 vs 0.89(0.21) g litre^–1). Free drug clearance was reduced inboth liver dysfunction groups compared with controls. ^*Department of Anesthesiology, Bowman-Gray Medical School, WinstonSalem, North Carolina, U.S.A.Department of Anaesthesia, Freeman Hospital, Newcastle uponTyne.Presented in part at the Anaesthetic Research Society meeting,Cardiff July 1989 [1].