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Bioavailability of hetacillin in rats after liver enzyme induction by various inducers with or without protein binding properties

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Summary

The serum levels and the half life of ampicillin derived from Hetacillin after administration of the latter to a total of 61 rats classified in 7 groups were determined. Each of these groups was pre-treated for 15 days with the following inducers ; phenobarbital, diphenylhydantoin, diazepam, chlorpromazine and phenylbutazone. The control group received saline. The d-glucaric acid concentrat ion in the urine prior to and after the administration of inducers and the liver weight were taken as enzyme induction indices.

Results showed a positive correlation between the indices of induction and the levels of ampicillin originating from hetacillin with a significant correlation coefficient between the serum levels of ampicillin and urine d-glucaric acid for all drugs studied.

The different effect of the various drugs indicated that they could be classified into the following two groups : a) those that induced a significant increase of the levels and half life (t1/2) of ampicillin. The effect was significant in decreasing order for phenylbutazone (r = 0,990), diazepam (r = 0,990) and diphenylhydantoin (r = 0,753). b) those which initially resulted in a significant increase of the levels of ampicillin and thereafter in a decrease with a significant shortening of its V/2 too. The effect was most significant for phenobarbital (r = 0,887) and less so for chlorpromazine (r = 0,800). Only for these two drugs was a significant and actually negative correlation observed between d-glucaric acid and tl/2 that is : phenobarbital (r = − 0,967) chorpromazine (r = − 0,752). Results suggest an interaction of Hetacillin and the above inducers.

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Authors and Affiliations

  1. Department of Experimental Pharmacology, Medical School, Athens University, 115 27, Athens, Greece

    M. Couvaris, P. Galanopoulou, Ch. Karageorgiou, H. Abdel Jalil & D. Varonos

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  1. M. Couvaris
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  2. P. Galanopoulou
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  3. Ch. Karageorgiou
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  4. H. Abdel Jalil
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  5. D. Varonos
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Couvaris, M., Galanopoulou, P., Karageorgiou, C. et al. Bioavailability of hetacillin in rats after liver enzyme induction by various inducers with or without protein binding properties. European Journal of Drug Metabolism and Pharmacokinetics 10, 27–32 (1985). https://doi.org/10.1007/BF03189694

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  • DOI: https://doi.org/10.1007/BF03189694

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