No abstract

The serum and urinary concentrations of pancuronium were measured in 14 surgical patients with cirrhosis and 12 patients free from liver disease undergoing abdominal surgery. A two-compartment open model was used in the pharmacokinetic analysis of the data. A two-fold increase in both the distribution half-life (T 1/2 alpha) from 11 min to 24 min and in the elimination half-life (T 1/2 beta) from 114 min to 208 min was observed in patients with cirrhosis. In these individuals, the total apparent volume of distribution of pancuronium was increased by 50%. Plasma clearance of pancuronium was decreased by 22%. No significant difference was found in the urinary excretion and biotransformation pattern of pancuronium. These results suggest that there is a risk of prolonged duration of action of pancuronium in patients with cirrhosis. In these patients, the initial dose to achieve adequate muscle relaxation is high and simultaneously there is slow disappearance of pancuronium from plasma. These alterations are mainly a consequence of the increase in the distribution volume of pancuronium in patients with cirrhosis.

The fate of pancuronium bromide has been investigated in 20 anaesthetized patients, seven undergoing cholecystectomy with choledochostomy (Group I), seven undergoing cholecystectomy only (Group 11) and six undergoing pelvic operations (Group 111). A fluorimetric method was used to determine pancuronium bromide and its bis-quaternary derivatives in blood, urine and bile. After a single intravenous injection of 6 mg pancuronium bromide, disappearance of the drug from the plasma proceeded in three phases with half-lives of < 5 min, 7-13 min and 108-147 min, respectively. Renal elimination is suggested as the major excretory pathway in man, but biliary excretion is also significant. Thirty hours after injection, the total recovery of unchanged pancuronium and its metabolite was approximately 37-44% in the urine (Groups I, 11, 111) and 11 yo in the bile (Group I).Only one metabolite (3-hydroxy derivative) of pancuronium bromide, accounting in total for about 15% of the administered dose, was identified in urine and 5 % in bile by thin-layer chromatography. Renal and hepatic elimination varied widely between patients.

No abstract

The renal and hepatic elimination and biotransformation, as well as the relation between disposition and duration of action of pancuronium and two of its analogues, dacuronium and ORG.6368, have been investigated in the cat. In pharmacokinetic studies, appreciable amounts of the latter two compounds were found in the urine, bile and liver 8 h after their intravenous administration. Various proportions of the injected dose of the respective drugs were metabolized. In another series of experiments it was shown that the early hepatic uptake (during the first 3 min after the injection) of ORG.6368 was significantly greater than that of dacuronium and pancuronium. The intensity and duration of action of the neuromuscular blocking effect of the three compounds were studied after intravenous and "close" intraarterial injection. On the basis of these pharmacokinetic and neuromuscular studies, it was concluded that the short duration of action of ORG.6368 is due primarily to its early hepatic uptake. The possibility cannot be excluded, however, that differences in the kinetics of the drug action of ORG.6368 and the other two compounds also contributed significantly to the differences seen in the duration of action of these compounds.