The effect of liver disease in man on the disposition of phenobarbital

J. Alvin, T. McHorse, A. Hoyumpa, M. T. Bush, S. Schenker

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57 Scopus citations

Abstract

The disposition of phenobarbital (PB) was studied in normal individuals and in patients with cirrhosis or acute viral hepatitis to determine if there is significant impairment of PB metabolism in hepatic disease and to what extent such abnormal disposition of the drug affects its disappearance from blood. The diagnosis of liver disease was based on characteristic clinical findings, biochemical liver 'function' tests and liver biopsy when necessary. All individuals had normal renal function and were free of other drug alcohol intake for at least 3 wk. With radiotracer methodology, PB and its principal metabolites, p hydroxyphenobarbital (PBOH) and conjugated PBOH (PHOC), were monitored in blood and urine for 5 days after a single dose of [ 14C] PB administered intraduodenally. PB blood half life [T(1/2)] in the control group was 86 ± 3 hr (S.E.). In cirrhotics the T(1/2) was prolonged to 130 ± 15 hr (P < 0.001) and this was accompanied by a 50% reduction in urinary PBOC excretion (P < 0.05). Urinary excretion of PB and PBOH was unaltered by cirrhosis. In patients with acute viral hepatitis, PB T(1/2) was not significantly prolonged and urinary excretion of PB and its metabolites was in the normal range (P < 0.05). No PBOH and only traces of PBOC were detected in the blood of either control individuals or patients with liver disease. Urinary excretion of unchanged PB was an important elimination pathway of the drug in all groups. As a result of this, PB T(1/2) in cirrhosis was only moderately prolonged.

Original languageEnglish (US)
Pages (from-to)224-235
Number of pages12
JournalJournal of Pharmacology and Experimental Therapeutics
Volume192
Issue number1
StatePublished - 1975
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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