Diphenhydramine disposition in chronic liver disease

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Abstract
Diphenhydramine (DPHM) disposition was examined in 9 patients with chronic alcohol-related liver disease and in 8 normal subjects. Sleep of 1-2 h duration was induced in all subjects by a 0.8 mg/kg i.v. dose without an apparent increase in cerebral sensitivity in the patients with cirrhosis. Protein binding as determined by equilibrium dialysis (3H-DPHM) revealed a 15% decrease in the cirrhotic patients, while recovery of unchanged DPHM in urine (2%) was of the same order in the 2 groups. Computerized biexponential curve analysis was used to compare the plasma profiles for 5 of the patients and 6 of the normal subjects. Monoexponential curve analysis of the terminal .beta.-phase, including all subjects, was also used to compare the 2 groups. The means of plasma clearance and apparent volume of distribution in cirrhotic patients were, respectively, less and greater than in normal subjects, but these differences were not significant. The t1/2 [half life] for the .beta.-phase (t1/2.beta.), which reflects this reciprocal trend, was increased in the patients (15.2 .+-. 1.5 and 9.3 .+-. 0.9 h). This correlated in part with severity of disease, with r = 0.723 between t1/2.beta. and the serum bilirubin levels. A single i.v. dose of DPHM provided safe and effective sedation in patients with cirrhosis.