Relative bioavailability of itraconazole from an extemporaneously prepared suspension and from the marketed capsules.
The bioavailability of itraconazole from an extemporaneously prepared suspension was compared with its bioavailability from the commercially available capsules. Ten healthy volunteers were fed breakfast and were then randomly assigned to receive either 400 mg of itraconazole 40-mg/mL oral suspension or four 100-mg itraconazole capsules with 240 mL of water. They were not allowed to rest in a supine position for six hours, eat for four hours, or take any beverages for two hours post-dose. Blood samples were taken immediately after the subjects had eaten and at intervals up to 72 hours post-dose. Serum was separated and stored at -70 degrees C. Serum itraconazole and hydroxyitraconazole concentrations were measured by high-performance liquid chromatography. After 14 days, each subject was given the dosage form that he or she did not previously receive, and testing was repeated. Maximum concentration (Cmax) and time to reach maximum concentration (tmax) were determined, and the area under the serum concentration-versus-time curve from 0 to 72 hours (AUC0-72) was estimated. The suspension:capsule ratios of least-squares means for Cmax, tmax, and AUC0-72 for itraconazole were 0.15 (90% confidence interval [CI], 0.11-0.21), 0.95 (90% CI, 0.75-1.20), and 0.12 (9% CI, 0.06-0.23), respectively. The results for hydroxyitraconazole were similar: 0.19 (0.13-0.28), 0.95 (0.81-1.12), and 0.13 (0.07-0.23), respectively. The bioavailability of itraconazole from the extemporaneously prepared suspension is much lower than that from capsules.
Christensen
K J
KJ
Critical Care and Internal Medicine, University of Arkansas for Medical Sciences Medical Center, Little Rock 72205, USA. christensenkeithj@exchange.uams.edu
Gubbins
P O
PO
Gurley
B J
BJ
Bowman
J L
JL
Buice
R G
RG
D000328:Adult; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002214:Capsules; D004339:Drug Compounding; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013535:Suspensions; D013810:Therapeutic Equivalency
D000935:Antifungal Agents; D002214:Capsules; D013535:Suspensions; D017964:Itraconazole