Multiple-Dose Pharmacokinetics of Ketoconazole Administered Orally to Gopher Tortoises (Gopherus polyphemus)

• Published in: Journal of zoo and wildlife medicine 1991-06, Vol.22 (2), p.191-198
• Main Authors: Page, C. Douglas, Mautino, Michele, Derendorf, Hartmut, Mechlinski, Withold
• Format: Article
• Language: English
• Subjects: Blood; Blood plasma; Dosage; Fungal infections; Half lives; Human resources; Medication administration; Pharmacokinetics; Tortoises; Zoos
• ISSN: 1042-7260; 1937-2825

Multiple dosing pharmacokinetics of ketoconazole were determined after oral administration of the drug at two dosage levels (15 mg/kg and 30 mg/kg) to captive gopher tortoises (Gopherus polyphemus). Using a crossover experimental design, eight tortoises were dosed at each level every 24 hr for 72 hr. Prior to drug dosage, the health status of each tortoise was assessed by physical examination and measurements of body weight to carapace length ratio, serum chemistries, hematocrit, and total plasma protein concentration. Overt toxic effects of ketoconazole were evaluated by repetition of these measurements during sample collection and 72 hr after initial drug administration. Plasma concentrations of ketoconazole were measured using high performance liquid chromatography on blood samples collected via venous catheterization before and &gt78 hr after drug administration. At the 15 mg/kg dosage level, the rising plasma concentration phase (RPCP) half-life was 1.5 ± 1.4 hr and the falling plasma concentration phase (FPCP) half-life was 13.2 ± 1.7 hr. At the 30 mg/kg dosage level, the RPCP half-life was 0.3 ± 0.1 hr and the FPCP half-life was 14.4 ± 2.5 hr. Both doses resulted in therapeutic concentrations of drug in plasma at steady state. No hematologic or serum chemistry alterations attributable to drug toxicity were detected.