Effect of upper abdominal surgery and cirrhosis upon the pharmacokinetics of methohexital.

Abstract

The pharmacokinetic profile of methohexital was studied in cirrhotic patients (n = 8), patients undergoing upper abdominal surgery (n = 8) and orthopaedic patients under general anaesthesia (n = 8). The total plasma clearance of methohexital was unchanged in cirrhotics: 54 +/- 22 l.h-1 (mean +/- s.d.) as well as in patients undergoing upper abdominal surgery: 60 +/- 14 l.h-1 in comparison to orthopaedic surgery: 70 +/- 24 l.h-1. The central volume and total volume of distribution and the distribution and elimination half-lives were similar between the three groups. Despite its hepatic dependent elimination, methohexital elimination kinetics were unchanged in patients undergoing upper abdominal surgery and in cirrhosis. Owing to the high hepatic extraction ratio of methohexital, its elimination should be influenced by the hepatic blood flow. The unchanged elimination kinetics presently observed in patients with cirrhosis or those undergoing upper abdominal surgery suggest that the hepatic blood flow is less diminished than expected in these patients.