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Abstract

PHARMACOKINETIC INTERACTIONS AND PHARMACOKINETIC PHARMACODYNAMIC SURROGATE RELATIONSHIPS OF ENROFLOXACIN AND DICLOFENAC IN BUFFALO CALVES FOLLOWING INTRAVENOUS ADMINISTRATION

Nitesh Kumar* and Challapa Jayachandran

ABSTRACT

Clinical relevance of pharmacokinetic interactions of enrofloxacin and diclofenac were studied in five female buffalo calves to know about the merit of the combination. Enrofloxacin (4 mg/kg) were administered intravenously separately and in combination. Between each injection an interval of 3 weeks were allowed in order to eliminate the drug(s) from the body. Samples of plasma and urine were collected at predetermined time intervals, extracted and analyzed by High Performance Liquid Chromatography while urine samples of enrofloxacin were analyzed by microbiological assay. Pharmacokinetic evaluation of plasma concentrations versus time profile of enrofloxacin and diclofenac was performed by using two-compartment open model whereas ciprofloxacin (active metabolite of enrofloxacin) was analyzed by using non-compartmental analysis. All kinetic parameters of enrofloxacin and its metabolite ciprofloxacin when enrofloxacin given alone and together with diclofenac did not differ significantly which denote that diclofenac may not have any influence in distribution, metabolism and elimination of enrofloxacin. The ratios of enrofloxacin metabolized to ciprofloxacin were 0.47 and 0.42 when enrofloxacin was given alone and together with diclofenac, respectively. In contrast, some of the important kinetic parameters of diclofenac differed significantly in combined administration. The rate of distribution of diclofenac was not affected by enrofloxacin as shown by non-significant difference in distribution half life values when diclofenac was given alone and together with enrofloxacin. Significantly (p<0.01) higher elimination half life, mean residence time and volume of distribution values of 12.84 1.29 h, 18.07 1.92 h and 1.34 0.04 L/kg were obtained when diclofenac was given together with enrofloxacin as compared to the values of 4.06 0.59 h, 4.72 0.85 h and 0.54 0.10 L/kg respectively, when diclofenac was given alone. No effect of diclofenac on the pharmacokinetics of enrofloxacin in buffalo calves when both drugs were given in combination. In contrast, enrofloxacin influenced some of the important kinetic parameters of diclofenac when both the drugs were given together. Therefore, we conclude that enrofloxacin can be used safely and effectively with diclofenac in clinical cases of drug sensitive microbial infections accompanied by any other inflammatory conditions in buffalo species.

Keywords: Pharmacokinetic interactions, Pharmacodynamic efficacy, enrofloxacin, diclofenac, buffalo calves.


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