Relative bioavailability of itraconazole from an extemporaneously prepared suspension and from the marketed capsules

Abstract

The bioavailability of intraconazole 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 intraconazole 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°C. Serum intraconazole 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 (C(max)) and time to reach maximum concentration (t(max)) were determined, and the urea under the serum concentration-versus-time curve from 0 to 72 hours (AUC0-72) was estimated. The suspension: capsule ratios of least-squares mean for C(max') t(max') 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.