Impaired hepatic drug metabolism after jejunoileal bypass in rats

D. J. Tuma, J. A. Vanderhoof, Michael Floyd Sorrell

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Abstract

The effects of jejunoileal bypass on hepatic drug metabolism were studied. An 85% jejunoileal bypass similar to the type performed in man for the treatment of morbid obesity was performed in adult, male Sprague-Dawley rats. A second group of rats received a sham operation and was pair-fed to the bypassed group. A third group was similarly sham-operated and fed ad libitum. The animals in the bypassed group lost 20% of their original body weight after 2 weeks and then maintained this reduced weight for the duration of the 2 month experimental period. Both groups of sham-operated controls gained weight although the pair-fed group grew at a slower rate due to a reduced dietary intake. Cytochrome P-450 content and the activities of cytochrome c reductase, aniline hydroxylase, pentobarbital hydroxylase and glucose 6-phosphatase in hepatic microsomes were significantly decreased in the bypassed rats compared to both control groups when the results were expressed per milligram of microsomal protein. When the data were corrected for microsomal recovery and expressed per 100 g b.wt., decreased cytochrome P-450 content and lowered activities of microsomal enzymes were also observed in the bypassed rats. No significant differences were observed between the control groups. Furthermore, the metabolism of aniline and pentobarbital by liver slices isolated from bypassed rats was impaired. These findings demonstrate impaired hepatic drug metabolism after jejunoileal bypass in the rat and suggest caution in drug administration to patients after bypass.

Original languageEnglish (US)
Pages (from-to)167-171
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume206
Issue number1
StatePublished - Jan 1 1978

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Jejunoileal Bypass
Liver
Pharmaceutical Preparations
Cytochrome P-450 Enzyme System
Aniline Hydroxylase
Cytochrome Reductases
Weights and Measures
Glucose-6-Phosphatase
Control Groups
Morbid Obesity
Pentobarbital
Microsomes
Cytochromes c
Sprague Dawley Rats
Body Weight
Enzymes
Proteins

ASJC Scopus subject areas

  • Pharmacology

Cite this

Impaired hepatic drug metabolism after jejunoileal bypass in rats. / Tuma, D. J.; Vanderhoof, J. A.; Sorrell, Michael Floyd.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 206, No. 1, 01.01.1978, p. 167-171.

Research output: Contribution to journalArticle

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