title: Comparative study of the effects of some inducers with or without protein binding properties on bioavailability of isoxazolylpenicillins in rats.
abstract: The effect of various inducers with or without protein binding properties on serum levels and half life of Oxacillin, Cloxacillin and Dicloxacillin was studied. A total of 102 male rats classified in 3 "categories" according to the administered penicillin with 6 groups of rats in each of them were used. Each group was pretreated for 15 days with the following inducers: phenobarbital, diphenylhydantoin, diazepam, chlorpromazine and phenylbutazone. The control groups 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. The results showed a decrease of serum levels and half life of three penicillins with a negative correlation between urine d-glucaric acid and serum penicillin levels. Phenobarbital, diphenylhydantoin and chlorpromazine affected the 3 penicillins in the following statistically significant order: oxacillin, dicloxacillin, cloxacillin. Diazepam affected: cloxacillin, dicloxacillin, oxacillin, and phenylbutazone: dicloxacillin, cloxacillin and oxacillin. However all drugs finally produced a uniform effect on all 3 penicillins in the following decreasing order: phenobarbital (r = -0.910), diphenylhydantoin (r = -0.864), phenylbutazone (r = -0.851), chlorpromazine (r = -0.842) and diazepam (r = -0.821). For all inducers, the effect was most significant for oxacillin (r = -0.869), second most significant for dicloxacillin (r = -0.811) and finally for cloxacillin (r = -0.778). The results suggested an interaction of isoxazolylpenicillins and the above drugs.
mesh_terms: D000818:Animals; D001682:Biological Availability; D002746:Chlorpromazine / Q000494:pharmacology; D003023:Cloxacillin / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D004009:Dicloxacillin / Q000378:metabolism*; D004790:Enzyme Induction; D006207:Half-Life; D008099:Liver / Q000201:enzymology; D008297:Male; D010068:Oxacillin / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D010653:Phenylbutazone / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D010672:Phenytoin; D004009:Dicloxacillin; D010653:Phenylbutazone; D003023:Cloxacillin; D003975:Diazepam; D002746:Chlorpromazine; D010068:Oxacillin; D010634:Phenobarbital