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 language | English (US) |
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Pages (from-to) | 167-171 |
Number of pages | 5 |
Journal | Journal of Pharmacology and Experimental Therapeutics |
Volume | 206 |
Issue number | 1 |
State | Published - Jan 1 1978 |
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ASJC Scopus subject areas
- Molecular Medicine
- 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 journal › Article
}
TY - JOUR
T1 - Impaired hepatic drug metabolism after jejunoileal bypass in rats
AU - Tuma, D. J.
AU - Vanderhoof, J. A.
AU - Sorrell, Michael Floyd
PY - 1978/1/1
Y1 - 1978/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0017852392&partnerID=8YFLogxK
M3 - Article
C2 - 660546
AN - SCOPUS:0017852392
VL - 206
SP - 167
EP - 171
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 1
ER -