title: Bioavailability of hetacillin in rats after liver enzyme induction by various inducers with or without protein binding properties.
abstract: 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 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 t1/2 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 t1/2 that is: phenobarbital (r = -0,967) chlorpromazine (r = -0,752). Results suggest an interaction of Hetacillin and the above inducers.
mesh_terms: D000667:Ampicillin / Q000097:blood / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D004790:Enzyme Induction / Q000187:drug effects; D005937:Glucaric Acid / Q000652:urine; D006207:Half-Life; D008099:Liver / Q000201:enzymology*; D008297:Male; D009929:Organ Size; D010406:Penicillins / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D010406:Penicillins; D000667:Ampicillin; D005937:Glucaric Acid; C100115:hetacillin