Vol 55 Feb 1 1998 Am J Health-Syst Pharm 261 Itraconazole Reports EPO RTS R Street, Little Rock, AR 72205, or to christensenkeithj@exchange. uams.edu. Itraconazole (Sporanox) was provided by Janssen Pharmaceu- tica, Inc., Titusville, NJ; methanolic standards of itraconazole and hydroxyitraconazole were provided by Janssen Research Founda- tion, Beerse, Belgium; and sapraconazole was provided by Janssen Biotech NV, Olen, Belgium. Presented at the ASHP Midyear Clinical Meeting, New Orleans, LA, December 11, 1996. Copyright © 1998, American Society of Health-System Phar- macists, Inc. All rights reserved. 1079-2082/98/0201-0261$06.00. KEITH J. CHRISTENSEN, PH ARM.D., is Clinical Pharmacy Specialist, Critical Care and Internal Medicine, University of Arkansas for Medical Sciences (UAMS) Medical Center, and Clinical Assistant Professor of Pharmacy Practice, College of Pharmacy, UAMS, Little Rock. PAUL O. GUBBINS, PH ARM.D., is Assistant Professor of Phar- macy Practice—Infectious Disease; BILL J. GURLEY, PH.D., is Associ- ate Professor of Pharmaceutics; and JASO N L. BOWMAN is Doctor of Pharmacy Candidate, College of Pharmacy, UAMS. RO BERT G. BUICE, PH.D., is Director, Biopharmaceutics and Pharmacokinet- ics, Zenith Laboratories, Inc., Northvale, NJ. Address reprint requests to Dr. Christensen at Department of Pharmacy, Slot 571, UAMS Medical Center, 4301 W. Markham Relative bioavailability of itraconazole from an extemporaneously prepared suspension and from the marketed capsules KEITH J. CHRISTENSEN, PAUL O. GUBBINS, BILL J. GURLEY, JASO N L. BOWMAN, AND RO BERT G. BUICE Abstract: The bioavailability of itraconazole from an extem- poraneously prepared suspen- sion was compared with its bioavailability from the com- mercially available capsules. Ten healthy volunteers were fed breakfast and were then randomly assigned to re- ceive either 400 mg of itra- conazole 40-mg/mL oral suspension or four 100-mg itraconazole capsules with 240 mL of water. They were not allowed to rest in a su- pine position for six hours, eat for four hours, or take any beverages for two hours post- dose. Blood samples were tak- en immediately after the sub- jects had eaten and at intervals up to 72 hours post- dose. Serum was separated and stored at –70 °C. Serum itraconazole and hydroxyitra- conazole concentrations were measured by high- performance liquid chroma- tography. After 14 days, each subject was given the dosage form that he or she did not previously receive, and test- ing was repeated. Maximum concentration (C max ) and time to reach maximum concen- tration (t max ) were deter- mined, and the area under the serum concentration- versus-time curve from 0 to 72 hours (AUC 0–72 ) was esti- mated. The suspension:capsule ra- tios of least-squares means for C max , t max , and AUC 0–72 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 hydroxyitracona- zole 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 itra- conazole from the extempo- raneously prepared suspen- sion is much lower than that from capsules. Index terms: Antifungals; Blood levels; Capsules; Com- pounding; Costs; Drugs, availability; Equivalency; Hy- droxyitraconzole; Itracona- zole; Metabolism; Sucrose; Suspensions Am J Health-Syst Pharm. 1998; 55:261-5 traconazole is a triazole antifungal agent indicated for the treatment of aspergillosis, histoplasmosis, and blastomycosis in immunocompromised and nonimmunocompromised patients. Absorption is highly variable and is increased by the presence of food and low gastric acidity. 1-4 The currently available 100- mg capsule containing itraconazole-coated pellets is dif- ficult to administer to some patients (e.g., those receiving I medications via a nasogastric or gastrostomy tube, those undergoing bone marrow transplantation), and thera- peutic alternatives for such patients are limited. More- over, dose-standardization difficulties make the capsule less than practical for pediatric use. Thus, the need for a liquid oral dosage form is clear. The recent release of an itraconazole solution formulated with a hydroxypropyl- β-cyclodextrin vehicle (Sporanox oral solution, Janssen)