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

, : Bioavailability of hetacillin in rats after liver enzyme induction by various inducers with or without protein binding properties. European Journal of Drug Metabolism & Pharmacokinetics 10(1): 27-32

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 concentration 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 2 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 t1/2 too. The effect was most significant for phenobarbital (r = 0.887) and less so for chlorpromazine (r = 0.800). Only for these 2 drugs was a significant and actually negative correlation observed between d-glucaric acid and t1/2 that is: phenobarbital (r = -0.967) chorpromazine (r = -0.752). Results suggest an interaction of Hetacillin and the above inducers.


PMID: 4029217

DOI: 10.1007/bf03189694

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