Population pharmacokinetics of itraconazole solution after a single oral administration in captive lesser flamingos (Phoeniconaias minor)

Abstract

Aspergillosis is an infectious, non‐contagious fungal disease of clinical importance in flamingo collections. Itraconazole is an antifungal drug commonly used in the treatment and prophylaxis of avian aspergillosis. Studies have shown that dosage regimes in birds vary based on different itraconazole presentation and administration methods. This investigation used a population pharmacokinetic approach to study itraconazole in lesser flamingos. Itraconazole was administered orally at 10 mg/kg to 17 flamingos. A sparse blood sampling was performed on the subjects, and samples were collected at 1, 2, 3, 5, 8, 12, 16, 21, and 24 hr post‐drug administration. Twelve flamingos were sampled three times, three birds bled twice and two sampled once. Itraconazole in plasma was quantified using high‐pressure liquid chromatography (HPLC). A one‐compartment pharmacokinetic model with first order absorption was fitted to the data using nonlinear mixed effects modeling (NLME) to determine values for population parameters. We identified a long half‐life (T½) of more than 75 hr and a maximum plasma concentration (CMAX) of 1.69 µg/ml, which is above the minimal inhibitory concentrations for different aspergillus isolates. We concluded that plasma drug concentrations of itraconazole were maintained in a population of flamingos above 0.5 ug/ml for at least 24 hr after a single oral dose of 10 mg/kg of itraconazole solution.

A brief review on models for birds exposed to chemicals

“…Half of the 130 papers focused on granivores (namely, seed-eating birds (Anadón et al, 2011;Fournier et al, 2015;Pollet et al, 1985)). Among wild species, groups of carnivores (i.e., predatory birds, such as raptors (Azmanis et al, 2021;Engelman et al, 2012;Rattner et al, 2020)) and piscivores (i.e., birds foraging for and eating fish or other sea life (An et al, 2006;Goutte et al, 2018;Sánchez et al, 2019)) are similarly represented (between 9 and 14 %) (Figure 3, upper panel). A bit less than one third of the papers investigated drugs, while around 20% of them focused on PPP (Figure 3, lower panel).…”