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.