Effect of food on the pharmacokinetics of a new hydroxypropyl-beta-cyclodextrin formulation of itraconazole.
OBJECTIVE
To compare the pharmacokinetics of a single 100-mg oral dose of itraconazole administered as 10 ml of a 10-mg/ml itraconazole solution in hydroxypropyl-beta-cyclodextrin under fasting versus postprandial conditions.


METHODS
Open-label, two-way, randomized, crossover study.


METHODS
Janssen Research Foundation, Belgium.


METHODS
Twelve healthy volunteers.


METHODS
Blood samples were obtained for pharmacokinetic analyses immediately before dosing and at regular intervals up to 96 hours after each dose. Blood and urine samples were obtained for hematologic, biochemical, and urinary safety analyses at baseline and at the end of the study.


RESULTS
The mean peak plasma concentrations of both itraconazole and its active metabolite hydroxy-itraconazole were significantly higher under fasting conditions than under postprandial conditions. The mean times to peak concentration for both the parent compound and its metabolite were significantly shorter under fasting than under nonfasting conditions. The mean areas under the curve (AUC0-infinity and AUC0-24 hrs) were also significantly higher under fasting than under postprandial conditions.


CONCLUSIONS
Our findings suggest that the higher bioavailability of this new formulation of itraconazole may be of benefit in seriously ill patients who are not able to ingest adequate quantities of food. The fact that the solution was also well tolerated and was not associated with clinically significant changes in any laboratory value further underscores the potential utility of this dosing form.
Van de Velde
V J
VJ
Department of Drug Metabolism and Pharmacokinetics, Janssen Research Foundation, Beerse, Belgium.
Van Peer
A P
AP
Heykants
J J
JJ
Woestenborghs
R J
RJ
Van Rooy
P
P
De Beule
K L
KL
Cauwenbergh
G F
GF
D000328:Adult; D000704:Analysis of Variance; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D003912:Dextrins / Q000008:administration & dosage*; D004304:Dosage Forms; D016503:Drug Delivery Systems; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008875:Middle Aged
D000935:Antifungal Agents; D003912:Dextrins; D004304:Dosage Forms; D017964:Itraconazole