Hepatic encephalopathy and altered cimetidine kinetics

Cimetidine kinetics were followed in 16 cirrhotic patients after a single IV 300-mg dose. The patients were grouped according to a history of portal systemic encephalopathy (PSE). There were no differences among the groups in volume of distribution, biologic t 1 2, or distributional clearance. In cirrhotic patients with no history of PSE, cimetidine kinetics and metabolism were the same as in healthy subjects. Patients with a history of PSE (n = 8) had lower cimetidine total body clearance than cirrhotic patients without a history of PSE and healthy subjects. Cirrhotic patients with a history of PSE also had decreased formation of cimetidine sulfoxide (as judged by differences in the sulfoxide serum concentration-time AUC). Because of the 40% decrease in total clearance, dosage in cirrhotic patients with a history of PSE should be reduced to minimize the risk of CNS side effects associated with cimetidine.