Paracetamol (acetaminophen) clearance in patients with cirrhosis of the liver

The pharmacokinetics of paracetamol were studied in 11 patients with cirrhosis of the liver and 12 controls. The average biological half-life after oral administration of 1 g paracetamol was significantly prolonged in patients with hepatic cirrhosis compared to the controls (3.7 hr vs.2.1 hr) and, correspondingly, the average plasma clearance was significantly reduced from 337 ml x min-1 in the controls to 162 ml x min-1 in the patients with cirrhosis of the liver. After subchronic dosing of paracetamol with 1 g paracetamol t. i. d. the plasma half-lives of paracetamol remained unchanged. Steady-state levels of paracetamol were significantly increased in the patients with cirrhosis of the liver. A significant correlation between the values of plasma clearance of paracetamol and prothrombin time (r = +0.88), galactose elimination capacity (r = +0.66), plasma albumin (r = +0.85) was found. No clinical or biochemical signs of hepatotoxicity were observed during the study.