Preliminary Pilot Study of Itraconazole After a Single Oral Dose of a Veterinary Formulation Solution in African Penguins (Spheniscus demersus).

Aspergillosis is a common cause of morbidity and mortality in captive penguins. Itraconazole, an antifungal drug, is commonly used to treat aspergillosis infections in avian species; however, commercially available human formulations are costly, and studies have shown the effectiveness of compounded formulations to be unreliable. The US Food and Drug Administration (FDA) recently approved a veterinary formulation of itraconazole, Itrafungol, for use in cats. This study provides preliminary results from limited sampling evaluating whether this veterinary formulation is suitable for future studies in the African penguin (Spheniscus demersus). A 20 mg/kg PO itraconazole dose was administered to 9 African penguins. Blood samples were taken over the course of 24 hours; each sample was collected from a different bird to minimize stress to the animals. Plasma was analyzed by high-performance liquid chromatography for concentrations of itraconazole. The drug was absorbed in all penguins, and plasma concentrations in 5 of 9 penguins (56%) were found to be greater than the established therapeutic dose of 1.0 µg/ mL. To our knowledge, this is the first study that has investigated a 20 mg/kg dose of itraconazole in a penguin species. The small sample size limits the conclusions that can be drawn from this preliminary study. Nonetheless, we demonstrate encouraging evidence that the FDA-approved formulation of oral itraconazole solution should be considered for future study as a cost-effective treatment for aspergillosis in African penguins and other avian species.

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

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.

Prediction of crew health effects from air samples taken aboard the International Space Station.

INTRODUCTION: Spaceflight aboard the International Space Station (ISS) involves stays of individual crewmembers for up to 6 mo during which they are exposed to a complex mixture of airborne pollutants. Methods to predict specific health effects from exposure to a mixture of air pollutants are not well developed. Herein, air monitoring data from the ISS are used to demonstrate a new method to estimate a threshold for possible health effects from exposure to mixtures. METHODS: An empirical, additive approach was developed to transform monthly air pollutant data, which had been obtained primarily by gas chromatography-mass spectrometry from samples of ISS air, to threshold (T) values for 16 adverse health effect groups. Spacecraft maximum allowable concentrations (SMACs), available for most spacecraft air pollutants, were used to form target-organ/effect groups, from which group T values were estimated. If T >1 for a group, then there is an unacceptable risk of the toxic effect. RESULTS: Samples of air taken from the ISS in 2010 revealed that all 16 toxicological groups were within safe limits. Highest T values were as follows: mucosal irritants (0.53 +/- 0.44), headache (0.52 +/- 0.06), central nervous system depression (0.25 +/- 0.06), and cardiac sensitization (0.13 +/- 0.04). DISCUSSION: The additive model is supported by limited inhalation data on rats in the literature. Our predictions of no adverse effect on crew health are useful as part of NASA's Lifetime Surveillance of Astronaut Health (LSAH). If one of the 16 levels had exceeded T=1, then standard surveillance could be supplemented to address this potential health risk.