Effect of intramuscular diclofenac sodium on pharmacokinetics of intravenous enrofloxacin in calves

Interactions between nonsteroidal antiinflammatory drugs (NSAIDs) and other drugs occur relatively frequently because of the wide use of the former. Enrofloxacin, a fluoroquinolone antimicrobial approved exclusively for veterinary use has a broad spectrum of antibacterial activity and is used in the treatment of septicemia, respiratory tract, urinary tract, skin, soft tissue, bone and joint infections etc. Diclofenac sodium, a nonsteroidal antiinflammatory drug is commonly used for the therapeutic management of pain, inflammatory conditions, rheumatoid arthritis and related disorders. Clinicians often prescribe both, an antimicrobial agent and an antiinflammatory agent at the same time to get the desired effect in animals. Since there are many reports of drug interaction among the NSAIDs and fluoroquinolone compounds, it was thought worthwhile to study the effect of diclofenac sodium on the pharmacokinetics of enrofloxacin, to assess the safety and/or potential toxicity. The study was conducted in six healthy calves in two phases (n=6 per group) by a cross over design with adequate wash out period of 21 days between each trial. In both the phases enrofloxacin was administered intravenously into left jugular vein at the dose of 5 mg/kg body weight. In the second phase diclofenac sodium was injected intramuscularly (1 mg/kg) in the gluteal region, half an hour before administration of enrofloxacin. The same animals were used again for diclofenac sodium co-administration with enrofloxacin after sufficient washout period. Blood samples (2-3 ml) were collected by jugular venepuncture into heparinised tubes. The samples prior to and after administration of drug were collected at various time intervals up to 96 hours following enrofloxacin administration. Plasma was harvested by centrifugation at 3000 rpm for 15 min and stored at –5 °C till analysis for enrofloxacin. For quantitative determination of enrofloxacin in plasma, HPLC method [1] was followed with some modifications. Plasma concentrations versus time data of enrofloxacin obtained during the study were utilized for calculating various pharmacokinetic parameters using noncompartmental method of analysis. Differences between respective means of pharmacokinetic parameters were evaluated using Student’s ‘t ’ test. P values <0.01 were considered to be statistically significant. The various pharmacokinetic parameters calculated by the non compartmental method of analysis after enrofloxacin alone and with diclofenac sodium are presented in Table 1. The elimination half-life (t 1⁄2 ) of enrofloxacin was found to be 1.38±0.05 h as compared to 1.01 h in dairy cows. However, a slightly longer t 1⁄2 of 1.7 h in lactating cows of Ayrshire breed was reported. The elimination half-life (t 1⁄2 ) in diclofenac sodium pretreated calves was 1.67±0.13 h, which Effect of intramuscular diclofenac sodium on pharmacokinetics of intravenous enrofloxacin in calves