Enhanced bioavailability of pethidine and pentazocine in patients with cirrhosis of the liver

Abstract

We studied the bioavailability and disposition kinetics of pethidine and pentazocine in patients with alcoholic cirrhosis and age-matched healthy subjects. In the presence of liver disease, the bioavailability of pethidine was 31% and pentazocine 233% greater than in normals. Systemic clearance was approximately half and terminal half-life double normal for both drugs, whereas volumes of distribution were unchanged. Because of greater bioavailability, oral doses of pethidine and pentazocine should be reduced substantially in patients with cirrhosis. When multiple oral or parenteral doses are required, dosing interval should be lengthened or repeated doses reduced below initial doses because of lower systemic clearance.