The effect of chronic administration of cyclosporin A on phenytoin pharmacokinetic parameters in the rat

Ibrahim A. Wasfi; Musbah O.M. Tanira

doi:10.1016/0024-3205(93)90140-X

The effect of chronic administration of cyclosporin A on phenytoin pharmacokinetic parameters in the rat

Ibrahim A. Wasfi^*, Musbah O.M. Tanira

^*Corresponding author for this work

Pharmacology & Clinical Pharmacy

Research output: Contribution to journal › Article › peer-review

Abstract

The potential for a drug interaction between cyclosporin A and phenytoin was investigated in rats. Rats were treated daily for 14 days with cyclosporin A (50mg/Kg, s.c.) and on the day of the experiment phenytoin (10mg/Kg) was administered intravenously. The mean residence time, the elimination half-life and the volume of distribution at steady state were significantly higher in the cyclosporin A-treated group than in the control group. However, total body clearance was similar in both groups. Plasma levels of urea, aspartate aminotransferase (AST) and glucose were significantly higher in the cyclosporin A-treated group than the control group. It was concluded that the observed changes could have been, at least in part, due to an inhibitory effect of cyclosporin A on liver drug metabolizing enzymes and/or liver and kidney damage.

Original language	English
Pages (from-to)	199-204
Number of pages	6
Journal	Life Sciences
Volume	52
Issue number	2
DOIs	https://doi.org/10.1016/0024-3205(93)90140-X
Publication status	Published - 1993

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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10.1016/0024-3205(93)90140-X

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abstract = "The potential for a drug interaction between cyclosporin A and phenytoin was investigated in rats. Rats were treated daily for 14 days with cyclosporin A (50mg/Kg, s.c.) and on the day of the experiment phenytoin (10mg/Kg) was administered intravenously. The mean residence time, the elimination half-life and the volume of distribution at steady state were significantly higher in the cyclosporin A-treated group than in the control group. However, total body clearance was similar in both groups. Plasma levels of urea, aspartate aminotransferase (AST) and glucose were significantly higher in the cyclosporin A-treated group than the control group. It was concluded that the observed changes could have been, at least in part, due to an inhibitory effect of cyclosporin A on liver drug metabolizing enzymes and/or liver and kidney damage.",

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N2 - The potential for a drug interaction between cyclosporin A and phenytoin was investigated in rats. Rats were treated daily for 14 days with cyclosporin A (50mg/Kg, s.c.) and on the day of the experiment phenytoin (10mg/Kg) was administered intravenously. The mean residence time, the elimination half-life and the volume of distribution at steady state were significantly higher in the cyclosporin A-treated group than in the control group. However, total body clearance was similar in both groups. Plasma levels of urea, aspartate aminotransferase (AST) and glucose were significantly higher in the cyclosporin A-treated group than the control group. It was concluded that the observed changes could have been, at least in part, due to an inhibitory effect of cyclosporin A on liver drug metabolizing enzymes and/or liver and kidney damage.

AB - The potential for a drug interaction between cyclosporin A and phenytoin was investigated in rats. Rats were treated daily for 14 days with cyclosporin A (50mg/Kg, s.c.) and on the day of the experiment phenytoin (10mg/Kg) was administered intravenously. The mean residence time, the elimination half-life and the volume of distribution at steady state were significantly higher in the cyclosporin A-treated group than in the control group. However, total body clearance was similar in both groups. Plasma levels of urea, aspartate aminotransferase (AST) and glucose were significantly higher in the cyclosporin A-treated group than the control group. It was concluded that the observed changes could have been, at least in part, due to an inhibitory effect of cyclosporin A on liver drug metabolizing enzymes and/or liver and kidney damage.

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The effect of chronic administration of cyclosporin A on phenytoin pharmacokinetic parameters in the rat

Abstract

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