Intravenous administration of diazepam in patients

was 17-9 + 1-4 mg (M ± SEM) compared with 27 ± 5-4 mg in controls (p < 0 01). Dose correlated significantly with serum albumin (p < 0-05). Baseline mean dominant frequency (MDF) and slow wave index (SWI) significantly correlated with albumin (p < 0 01). After diazepam, the MDF decreased and SWI increased. The change was greatest at the time of maximal clinical response. It was greater in liver disease and was greatest in patients with previous hepatic encephalopathy. In spite of reduced dose requirements in liver disease, there was no significant difference in plasma concentration at the end of drug infusion. This might in part be explained by a significant dose dependent increase in volume of distribution (p < 0 01). Differences in EEG response at similar plasma concentrations suggested differences in cerebral sensitivity. The clearance of diazepam decreased in chronic liver disease and correlated with the serum albumin (p < 0 01) and also with the clearances of antipyrine (p < 0 001) indocyanine green (p < 0 001) and d-propranolol (p < 0 001).