Pharmacokinetics and toxicity of ciprofloxacin in adult horses

Yamarik, T. A., Wilson, W. D., Wiebe, V. J., Pusterla, N., Edman, J., Papich, M. G. Pharmacokinetics and toxicity of ciprofloxacin in adult horses. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2010.01167.x.Using a randomized, cross-over study design, ciprofloxacin was administered i.g. to eight adult mares at a dose of 20-mg/kg, and to seven of the eight horses at a dose of 5-mg/kg by bolus i.v. injection. The mean C₀ was 20.5-μg/mL (±8.8) immediately after i.v. administration. The C_max was 0.6-μg/mL (±0.36) at T_max 1.46-(±0.66)-h after the administration of oral ciprofloxacin. The mean elimination half-life after i.v. administration was 5.8-(±1.6)-h, and after oral administration the terminal half-life was 3.6-(±1.7)-h. The overall mean systemic availability of the oral dose was 10.5-(±2.8)%. Transient adverse effects of mild to moderate severity included agitation, excitement and muscle fasciculation, followed by lethargy, cutaneous edema and loss of appetite developed in all seven horses after i.v. administration. All seven horses developed mild transient diarrhea at 36-48 after i.v. dosing. All eight horses dosed intragastrically experienced adverse events attributable to ciprofloxacin administration. Adverse events included mild transient diarrhea to severe colitis, endotoxemia and laminitis necessitating euthanasia of three horses on humane grounds. The high incidences of adverse events preclude oral and rapid i.v. push administration of ciprofloxacin.