Inhibition of hepatic microsomal enzymes by chloramphenicol

H. R. Adams, E. L. Isaacson, B. S.S. Masters

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Abstract

Effects of acute in vivo treatment with chloramphenicol on in vivo and in vitro indices of drug biotransformation functions of hepatic microsomal enzymes were studied in mice. A 30-minute or 1-hour pretreatment with a single i.p. injection of chloramphenicol (1.0-200.0 mg/kg) consistently prolonged the duration of pentobarbital anesthesia in a dose-related manner. The duration of pentobarbital anesthesia was reduced by 4 days pretreatment with phenobarbital, but the relative (percent) prolongation of pentobarbital anesthesia by chloramphenicol was similar in phenobarbital-induced and noninduced mice. Similarly, the ethylmorphine N-demethylase and benzphetamine N-demethylase activities of the 78,000xg hepatic microsomal fraction were inhibited by 35 to 50% after in vivo treatment with chloramphenicol (100 mg/kg i.p.) in both phenobarbital-induced and noninduced mice. The microsomal concentrations of protein, cytochrome P-450, NADPH-cytochrome c (P-450) reductase and cytochrome b5 were not discernibly altered by the antibiotic; however, the type 1 substrate binding spectra associated with the binding of hexobarbital to cytochrome P-450 were consistently reduced in microsomes harvested from chloramphenicol-treated mice. These findings indicate that in vivo treatment with chloramphenicol inhibits the drug-metabolizing capabilities of phenobarbital-induced and noninduced liver microsomes and suggest that there is an interference by the antibiotic (or an active metabolite) with cytochrome P-450 function.

Original languageEnglish (US)
Pages (from-to)388-396
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume203
Issue number2
StatePublished - Dec 1 1977

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Adams, H. R., Isaacson, E. L., & Masters, B. S. S. (1977). Inhibition of hepatic microsomal enzymes by chloramphenicol. Journal of Pharmacology and Experimental Therapeutics, 203(2), 388-396.