TELL LA, CRAIGMILL AL, CLEMONS KV, STEVENS DA; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. M-357.

Univ. of California, Davis, Davis, CA.

BACKGROUND: Aspergillosis causes morbidity and mortality in wild and domesticated birds. Aspergillus fumigatus can become disseminated in avian patients. Intravenous therapy is problematic, and oral itraconazole (ITZ) is the drug of choice for prophylaxis and treatment. However, the bioavailability of oral ITZ has been minimally investigated and no studies using carrier molecules for enhancing bioavailability have been done in birds. METHODS: Thirty domestic mallard ducks were used as a prototype species to evaluate two oral formulations of ITZ. ITZ-A was prepared by solubilizing 100 mg capsules in 0.1N HCL and adding orange juice for final concentration of 10 mg/ml ITZ. ITZ-B was prepared as a stock of 25 mg/ml of ITZ in hydroxypropyl-beta-cyclodextrin (HPCD) and diluted to 10 mg/ml. Birds received a single oral dose (20 mg/kg) and blood samples collected at 0, 1, 2, 3, 4, 8, 16, and 24 hrs post-treatment. Concentrations of ITZ and OH-ITZ were measured in plasma by HPLC and compared with ITZ concentrations measured by bioassay. RESULTS: By bioassay, C[max] occurred at 4 h, and was 5.1 and 4.8 microg/ml for ITZ-A and ITZ-B, respectively. Each had a similar AUC[0-24] and an approximate t[1/2] of 14 h. By HPLC, measured concentrations were lower with C[max] at 1 h of 1.7 and 1.4 microg/ml for ITZ and at 4 h of 0.32 and 0.25 microg/ml for OH-ITZ, respectively; OH-ITZ AUC were equivalent for each formulation. HPLC showed a 7 h t[1 / 2] for ITZ and >/= 12 h for OH-ITZ. CONCLUSIONS: Both formulations resulted in therapeutic levels similar to those in humans given 200 mg of ITZ q12h. Measurement of activity as ITZ by bioassay showed 6-fold higher concentrations than HPLC. HPCD did not increase bioavailability of ITZ in ducks. Mallard ducks do not metabolize ITZ to OH-ITZ as readily as do humans. Additional studies of the efficacy of ITZ against avian aspergillosis are warranted.

Publication Types:

• Meeting Abstracts

Keywords:

• 2-hydroxypropyl-beta-cyclodextrin
• Animals
• Area Under Curve
• Aspergillosis
• Aspergillus fumigatus
• Biological Availability
• Ducks
• Humans
• Itraconazole
• beta-Cyclodextrins
• methods

Other ID:

• GWAIDS0024907

UI: 102264531

From Meeting Abstracts