Disposition of posaconazole after single oral administration in large falcons (Falco spp): Effect of meal and dosage and a non-compartmental model to predict effective dosage.

Posaconazole has been used anecdotally to treat aspergillosis in falcons resistant to voriconazole. In human medicine, it is used prophylactically in immunosuppressed human subjects with invasive pulmonary aspergillosis. So far, no studies have been performed in birds. The aim of this study was to evaluate the in-vivo pharmacokinetic behavior of oral posaconazole after a single administration in six large falcons (i.e gyrfalcons, saker falcons). Posaconazole oral suspension (Noxafil, 40 mg/ml, Schering-Plough) was administered per os without meal in a single dosage of 12.5 mg/kg in 3 falcons. A comparison was done in two more falcons, one with a natural fatty meal at the same single dose, and one with a natural fatty meal and a higher dosage (20 mg/kg). Finally, six falcons received posaconazole pre-dissolved in corn oil with a natural low-fat meal in the higher single dose (20 mg/kg). No side effects were observed in the falcons in any of the experiments. In starved state posaconazole was poorly absorbed, more so than in other species. As expected, absorption of posaconazole was higher with the administration of meal or in the presence of plant (corn) oil, with a fourfold increase in apparent bioavailability. Despite the preferential absorption in the presence of fat, for both dosing schemes the AUC24 : MIC ratio was lower than described in human medicine to achieve a therapeutic effect. The AUCinf : MIC which is an indicator of efficacy after steady-state, while variable, did indicate that the drug is worth trying when susceptibility testing shows to be the only effective drug. LAY ABSTRACT: The focus of this work is to determine the pharmacokinetic parameters of oral posaconazole in large falcons for the first time after a single dose. Posaconazole has higher bioavailability when administered with meal and fatty components. No adverse reactions have been observed. The ratio of the area under the curve (AUC24) to minimum inhibitory concentration was lower compared to the therapeutic level in human.

Pharmacokinetics of voriconazole after a single intramuscular injection in large falcons (Falco spp.).

Voriconazole is one of the main azoles used to treat invasive aspergillosis in falconry raptors and birds. Despite the fact that there are studies for oral and intravenous use of voriconazole in birds, there are none for its effect after intramuscular use. Empirical use of intramuscular voriconazole in falcons, indicated quicker therapy response than the oral one. Aim of this study is to evaluate the in vivo pharmacokinetic disposition of injectable voriconazole after a single intramuscular injection in large falcons (i.e., Gyrfalcons, Saker falcons, Peregrine falcons). No clinical side effects were observed in the falcons. Absorption of voriconazole was rapid (0.5-2 hours) and reached a plasma level (>1 µg/ml) which is above the minimal inhibitory concentration (MIC) for all known Aspergillus strains. This level was maintained for 16 to 20 hours, thus indicating that a single injection of 12.5 mg/kg is not enough if T > MIC is taken into consideration. On a newer aspect, according to the AUC24 unbound: MIC parameter would be indicated that this dose would be rather sufficient for most Aspergillus strains.