EFFECT OF FOOD ON THE PHARMACOKINETICS OF A NEW HYDROXYPROPYL-BETA-CYCLODEXTRIN FORMULATION OF ITRACONAZOLE

Study Objective. To compare the pharmacokinetics of a single 100-mg or al dose of itraconazole administered as 10 ml of a 10-mg/ml itraconazo le solution in hydroxypropyl-beta-cyclodextrin under fasting versus po stprandial conditions. Design. Open-label, two-way, randomized, crosso ver study. Setting, Janssen Research Foundation, Belgium. Patients. Tw elve healthy volunteers. Interventions. Blood samples were obtained fo r pharmacokinetic analyses immediately before dosing and at regular in tervals up to 96 hours after each dose. Blood and urine samples were o btained for hematologic, biochemical, and urinary safety analyses at b aseline and at the end of the study. Measurements and Main Results. Th e mean peak plasma concentrations of both itraconazole and its active metabolite hydroxy-itraconazole were significantly higher under fastin g conditions than under postprandial conditions. The mean times to pea k concentration for both the parent compound and its metabolite were s ignificantly shorter under fasting than under nonfasting conditions. T he mean areas under the curve (AUC(0-infinity) and AUC(0-24) hrs) were also significantly higher under fasting than under postprandial condi tions. Conclusions. Our findings suggest that the higher bioavailabili ty of this new formulation of itraconazole may be of benefit in seriou sly ill patients who are not able to ingest adequate quantities of foo d. The fact that the solution was also well tolerated and was not asso ciated with clinically significant changes in any laboratory value fur ther underscores the potential utility of this dosing form.