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Comparative study of the effects of some inducers with or without protein binding properties on bioavailability of isoxazolylpenicillins in rats

  • M. Couvaris
  • P. Galanopoulou
  • Ch. Karageorgiou
  • S. Theodosopoulos
  • D. Varonos
Original Papers

Summary

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.

Key-words

Enzyme induction Protein binding Bioavailability Isoxazolylpenicillins Oxacillin Cloxacillin Dicloxacillin Phenobarbital Diphenylhydantoin Chlorpromazine Diazepam Phenylbutazone 

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Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • M. Couvaris
    • 1
  • P. Galanopoulou
    • 1
  • Ch. Karageorgiou
    • 1
  • S. Theodosopoulos
    • 1
  • D. Varonos
    • 1
  1. 1.Department of Experimental Pharmacology, Medical SchoolAthens UniversityAthensGreece

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