Designing voriconazole treatment for racing pigeons: balancing between hepatic enzyme auto induction and toxicity

Abstract

Aspergillosis is a major cause of mortality in captive birds and its prognosis is often poor due to treatment failure. Voriconazole is a novel triazole antifungal agent that may be useful for the treatment of this infection in birds as it has shown promise in other animal models of the disease. We examined the pharmacokinetic behaviour of voriconazole in racing pigeons (Columbia livia forma domestica). Intravenous, oral and aerosol administration were investigated in single (10 mg/kg BW PO; 10, 5, 2.5 mg/kg BW IV), multiple dose (10, 20 mg/kg BW PO q12h, q24h) and nebulization (15 min, 10 mg/ml NaCl 0.9%) experiments. Quantitative measurements of voriconazole in plasma, as well as in lung tissue, collected at several time points, were done with a validated high performance liquid chromatography method using ultraviolet detection. Designing a treatment schedule with voriconazole is complicated by dose-dependent pharmacokinetics and induction of its biotransformation. Moreover, hepatic changes were seen in the oral multiple dose regimen at 10 and 20 mg/kg BW twice a day. Taking all features into account our study suggests that the oral dosage schedules of 10 mg/kg BW twice a day or 20 mg/kg BW once a day could be most appropriate in treating pigeons with aspergillosis.