Hepatic and Renal Disposition of Pancuronium and Gallamine in Patients With Extrahepatic Cholestasis

Abstract

SUMMARYThe plasma clearance of pancuronium in patients with extrahepatic cholestasis was 16% lower than in a control group (1.47 ±0.11 mlmin"'kg" ' v. 1.76±0.21 mlmin"'kg"'), but the difference was not significant. A significant increase in the elimination half-life T± of pancuronium (from 141 to 224 min) and a significant increase in the volume of the peripheral compartment ( V 2 ) was found in patients with extrahepatic cholestasis when compared with control patients. There was a significantly lower cumulative biliary excretion of pancuronium (0.3±0.3% v. 10.9±3.2% in the controls) during the 48-h period of observation. The biotransformation and cumulative urinary excretion patterns of pancuronium revealed no significant differences between the two groups of patients. The increase of 7* + pancuronium in patients with extrahepatic cholestasis was mainly a consequence of the increase in the volume of distribution. No significant differences in the plasma clearance, 7*/ or in the volume of distribution were observed with gallnminr in the patients with extrahepatic cholestasis when compared with the control group. The cumulative urinary excretion of gallamine during 48 h in both groups of patients was approximately 100%. We concluded that in patients with cholestasis and normal glomerular nitration, gallamine is probably more reliable than pancuronium for neuromuscular blockade.

Clinical Pharmacokinetics of Neuromuscular Blocking Drugs

“…1981). In contrast, biliary obstruction prolonged the t'hfj of pancuronium (Westra et al 1981) secondary to decreased CL and increased Yd. Hepatocellular disease had only slight effects on the CL of pancuronium (Duvaldestin et al 1978a), but prolonged the t'l211 due to an increased V d.…”