Itrakonazol till häst : en farmakokinetisk möjlighet?

Abstract: Itraconazole is a third generation azol, a fungicide which acts by inhibiting ergerosterol synthesis in the fungal cell membrane, and thereby disturbing fungal regeneration. It has proven to be less toxic, to have a broader spectrum of activity and to be more potent than its predecessor ketoconazole. Itraconazole is only available in therapheutics approved for human use. Pharmacokinetic studies has been performed in humans, dogs, cats and laboratory animals. Although itraconazole has been used tentatively with good effect against fungal infections in horses, no pharmacokinetic studies have yet been done. The aim of this pilot study was to get an indication if itraconazole from a pharmacokinetic point of view is a suitable therapeutic agent in equine mycosis. We wanted to make sure that the bioavailability for oral dosing seamed sufficient and that elimination half-life of itraconazol wasn´t too short for it to be used in a practical manner. Two healthy horses were given itraconazole (5 mg/kg) intravenously and orally. Bloodsamples were collected for 71 hours and serum analyses of itraconazole were made by high performance liquid chromatography (HPLC). Pharmacokinetic parameters obtained in this study indicate that itraconazole, from a pharmacokinetic aspect, is suitable for treatment of equine mycosis, considering the long treatment often required. Bioavailability was 33 % (mean, n=2) which is sufficient for the drug to be given orally. Terminal half-life after intravenous administration was 50h (mean, n=2) and therefore drug administration once daily would be adequate. Mean value (n=2) of volume of distrubution was 7 l/kg and of clearence 0,11/kg·h. This seems promising and an extended study including a greater number of horses should be performed to optimize dose regimen in horses.