Abstract
The Pharmacokinetic aspects of flunixin (FL) administered alone and in combination with enrofloxacin (EN), were studied in clinically healthy calves. The experiments were performed on two groups: FL alone {2.2 mg/kg,intramuscular (IM)}, and combination of FL (2.2 mg/kg, IM) and EN {2.5 mg/kg, IM}. Plasma concentrations of FL were determined using High Performance Liquid Chromatography (HPLC) method. Moreover, the effects of FL alone or in combination on liver and kidney functions were also assessed. Flunixin was rapidly absorbed intramuscularly with a half-life of absorption (t ) of 0.094 h and the peak plasma concentration (C ) was 1.27 g/mL was attained after 1/2ab max 0.49 h (T ). Enrofloxacin significantly altered the pharmacokinetics of FL by delaying its absorption and accelerate its max elimination from body. Significant increases (32%) in the area under the curve (AUC) and (37%) in the elimination rate constant (K ) from the central compartment and a significant decrease (27%) in the elimination half-life (t ) of FL el 1/2el were found following coadministration with EN, compared with administration of FL alone. The maximum plasma drug concentration (C ) showed significant increase (28%) following the coadministration of EN with FL as max compared to that following the administration of FL alone. It was concluded that the combination of FL and EN negatively altered the kinetics of FL and exaggerated the adverse effect on hepato-renal function in calves consequently; the concomitant use of FL and EN should be avoided in calves.
Highlights
Flunixin (FL) is nonsteroidal anti-inflammatory drug (NSAID) inhibiting cycloxygenase enzymes in the arachidonic acid cascade, block the formation of cycloxygenase derived eicosanoid inflammatory mediators (Landoni et al, 1995; Cheng et al, 1998)
Enrofloxacin significantly altered the pharmacokinetics of FL by delaying its absorption and accelerate its elimination from body
Significant increases (32%) in the area under the curve (AUC) and (37%) in the elimination rate constant (Kel) from the central compartment and a significant decrease (27%)
Summary
Flunixin (FL) is nonsteroidal anti-inflammatory drug (NSAID) inhibiting cycloxygenase enzymes in the arachidonic acid cascade, block the formation of cycloxygenase derived eicosanoid inflammatory mediators (Landoni et al, 1995; Cheng et al, 1998). Enrofloxacin (EN) is a fluorquinolone antibacterial drug, extensively used in veterinary medicine (Schroder, 1989), due to its broad spectrum of activity against Gram-negative, some Grampositive bacteria and mycoplasma species (Prescott & Yielding, 1990; Butaye et al, 1997; Pellerin et al, 1998). It has bactericidal activity at relatively low concentration, and high bioavailability following oral or parenteral administration (Dorfman, et al, 1995), with long serum half-life, it used once or twice daily (Abo-EL-Sooud, 2003). The present investigation was undertaken with the following objectives: (1) to establish the serum concentration time profile and pharmacokinetic parameters for FL after IM administration in calves; (2) to determine pharmacokinetic parameters for FL www.veterinaryworld.org
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