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Clin Pharmacol Ther. 1984 Apr;35(4):474-9.

Diphenhydramine disposition in chronic liver disease.


Diphenhydramine (DPHM) disposition was examined in nine patients with chronic alcohol-related liver disease and in eight normal subjects. Sleep of 1 to 2 hr duration was induced in all subjects by a 0.8 mg/kg iv 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 two groups. Computerized biexponential curve analysis was used to compare the plasma profiles for five of the patients and six of the normal subjects. Monoexponential curve analysis of the terminal beta-phase, including all subjects, was also used to compare the two 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 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 hr). This correlated in part with severity of disease, with r = 0.723 between t1/2 beta and the serum bilirubin levels. In conclusion, a single intravenous dose of DPHM provided safe and effective sedation in patients with cirrhosis.

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