Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after intravenous and oral administration.

The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, respectively. Plasma concentrations of posaconazole were quantified by validated high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady-state volume of distribution (Vss ) were 0.15 (0.13-0.18) L hr-1  kg-1 and 1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life (t1/2 ) after i.v. and p.o. administration was 7.90 (7.62-8.18) and 12.79 (11.22-16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (Cmax ; median: 0.72, range: 0.55-0.93 µg/ml) was achieved in 8 (range 6-12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25 ± 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas.

Effect of dietary iron content on hematologic and other measures of iron adequacy in dogs.

Eighteen 9- to 10-week old Beagles were fed casein-based diets (4,710 kcal of metabolizable energy/kg of body weight) containing either 12, 80, or 160 mg of iron/kg of diet. Growth and feed consumption were monitored throughout the 47-day study. Hematocrit (Hct), hemoglobin (Hb) concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), RBC numbers, erythrocyte protoporphyrin (EP) concentration, serum iron concentration, serum total iron-binding capacity (TIBC), and serum ferritin concentration were determined weekly. Growth rate and feed efficiency were not significantly influenced by dietary iron content. At 14 days, Hb concentration, Hct, MCV, MCH, RBC numbers, and serum iron concentration were significantly (P less than 0.05) lower in dogs fed the 12 mg/kg diet, and remained significantly low for the remainder of the study. Erythrocyte protoporphyrin concentration increased significantly (P less than 0.05) by 14 days in dogs fed the basal diet, and remained significantly high relative to that in dogs of the other dietary groups for the remainder of the study. Serum ferritin concentration decreased in dogs of the group fed the basal diet, with a significant (P less than 0.05) difference beyond day 42. Differences in Hct, MCH, MCV, or hemoglobin, serum iron, serum ferritin, or EP concentration were not found between groups fed 80 and 160 mg of iron/kg of diet. Liver nonheme iron content was significantly (P less than 0.05) affected by dietary iron content.