Abstract: Background – Isavuconazole is a new triazole antifungal drug used in invasive fungal infections in people. It could be an effective therapy for canine mold infections, but limited information is available regarding its use in dogs. Objectives – To evaluate the single-dose pharmacokinetics of intravenously and orally administered isavuconazole and its safety in dogs. Animals – Six healthy, adult dogs were recruited from a pet population. Methods – After 12-hour fasting, dogs received 186 mg isavuconazonium sulfate (100 mg isavuconazole equivalent) intravenously and orally with serial blood sampling over 28 days in a two-way, randomized, crossover design with an 8-week washout period. Plasma isavuconazole concentrations were measured by liquid chromatography-mass spectrometry and pharmacokinetic parameters were determined by non-compartmental analysis. Results – Isavuconazole was well tolerated in each phase. After intravenous administration, clearance, volume of distribution at steady state, and terminal half-life were 350 ± 112 mL/kg/h, 9.8 ± 4.5 L/kg, and 90 ± 44 h, respectively. After oral administration, the maximum concentration, time to maximum concentration, terminal half-life, and observed area under the curve were 0.60 ± 0.27 μg/mL, 6.73 ± 2.45 h, 125 ± 80 h, and 7.32 ± 2.38 μg*h/mL, respectively. Oral bioavailability was 81.4 ± 12.8%. Conclusions and clinical importance – These results suggest isavuconazole has a long half-life in dogs and is relatively well-absorbed orally when administered in the fasted state. Multidose and pharmacodynamic studies are warranted to establish a therapeutic regimen for isavuconazole in dogs.
