Diphenhydramine disposition in chronic liver disease

C. G. Meredith, C. D. Christian, R. F. Johnson, S. V. Madhavan, S. Schenker

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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 β-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 t 1 2 for the β-phase (t 1 2β), 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 t 1 2β and the serum bilirubin levels. In conclusion, a single intravenous dose of DPHM provided safe and effective sedation in patients with cirrhosis.

Original languageEnglish (US)
Pages (from-to)474-479
Number of pages6
JournalClinical Pharmacology and Therapeutics
Volume35
Issue number4
DOIs
StatePublished - Apr 1984
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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