Plasma Disappearance and Cerebral Effects of Chlorpromazine in Cirrhosis

Abstract

1. The plasma disappearance and cerebral effects of chlorpromazine were studied in twenty-four patients with compensated cirrhosis and in matched controls using a sensitive gas-liquid chromatography (g.l.c) technique to measure chlorpromazine. Plasma disappearance followed a double-exponential decay curve. No difference could be detected between cirrhotic and control groups, even when the effect of prior treatment with inducing drugs was considered, and only minor differences were observed when the elimination rate constants (kel) were calculated. 2. Chlorpromazine caused drowsiness in all subjects, together with slowing of EEG activity. The slowest activity, which was accompanied by impaired cerebration, occurred in those patients with a past history of encephalopathy in whom the value for the pretreatment skew mean-dominant-frequency was abnormally low. 3. The susceptibility of some patients with cirrhosis to chlorpromazine is probably due to increased sensitivity of cerebral neurones, rather than impaired hepatic drug metabolism.