Thiopental pharmacokinetics in patients with cirrhosis

Abstract

The effect of cirrhosis on the pharmacokinetics and plasma protein binding of thiopental was studied in eight patients with cirrhosis, aged (mean ± SD) 42 ± 11 yr, and nine patients with normal hepatic and renal function, aged 48 ± 12 yr, undergoing elective abdominal or orthopedic surgery. The total apparent volume of distribution at steady state was of 2.3 ± 0.5 l.kg-1 in the controls and of 3.5 ± 1.9 l.kg-1 in the patients with cirrhosis. Thiopental plasma clearance based upon total drug concentrations was 3.9 ± 1.2 ml.min-1.kg-1 in the normal group and did not differ significantly in the patients with cirrhosis: 4.4 ± 2.2 ml.min-1.kg-1. The elimination half-life was of 529 ± 97 min in controls and of 714 ± 252 min in the patients with cirrhosis. The thiopental free fraction was 14.5 ± 3.4% in the controls and was increased significantly to 25.2 ± 3.9% in the patients with cirrhosis. Thiopental intrinsic clearance was decreased insignificantly (P = 0.06) from 28.3 ± 9.0 ml.min-1.kg-1 in the controls to 18.2 ± 10.5 ml.min-1.kg-1 in those with cirrhosis, suggesting that these patients may have a decreased capacity for thiopental metabolism. These results suggest that the risk of a prolonged effect following thiopental administration appears unlikely in patients with cirrhosis.