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 wer e then randomly assigned to receive either 400 mg of itraconazole 40-m g/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 h ours, eat for four hours, or take any beverages for two hours post-dos e. Blood samples were taken en immediately after the subjects had eate n and at intervals up to 72 hours postdose. Serum was separated and st ored at -70 degrees C. Serum itraconazole and hydroxyitraconazole conc entrations were measured by high-performance liquid chromatography. Af ter 14 days, each subject was given the dosage form that he or she did not previously receive, and testing was repeated. Maximum concentrati on (C-max) and time to reach maximum concentration (t(max)) were deter mined and the area under the serum concentration-versus-time curve fro m 0 to 72 hours (AUC(0-72)) was estimated.The suspension:capsule ratio s of least-squares means for C-max, t(max), and AUC(0-72) for itracona zole 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 f or 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 itracona zole from the extemporaneously prepared suspension is much lower than that from capsules.