Introduction: Itraconazole (I) is an important therapeutic agent in the management of serious fungal infections, though adequate serum concentrations are necessary for clinical success. Bioavailability of itraconazole in capsule form has been problematic and can be reduced as much as 50% in AIDS patients with gastric hypoacidity. Itraconazole oral solution (IOS) has improved bioavailability when compared to the capsule formulation and unlike capsules, itraconazole oral solution absorption may not be acid-dependent. Objective: To determine the effect of omeprazole, an acid-suppressing proton pump inhibitor, on peak serum concentrations (Cmax) of itraconazole oral solution. Methods: We performed an open label, prospective, randomized, crossover study in healthy adult volunteers. Fifteen subjects each received 400 mg itraconazole oral solution after an overnight fast on 2 occasions, with at least a 7 day washout period between doses. Subjects were randomized to receive 40 mg omeprazole nightly for 7 days prior to either itraconazole oral solution dose 1 or 2. Serum samples were obtained prior to itraconazole oral solution dose, and then at 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose. Concentrations of itraconazole and hydroxyitraconazole, an active metabolite, were determined by HPLC. Results: Interim analysis of 9 subjects indicates that omeprazole significantly decreased the Cmax of itraconazole (mean 1.80 vs. 1.29 5g/mL, median difference between treatments =0.238 5g/mL, p<0.01, Wilcoxon Signed Rank). Cmax of hydroxyitraconazole (1.03 vs. 0.98 5g/mL, median difference=0.032 5g/mL, p=0.65) and time to Cmax (Tmax) for both itraconazole and hydroxyitraconazole were not significantly different between treatments (p=0.14,p=0.24, Wilcoxon Signed Rank). Conclusions: Our preliminary data suggest that concurrent administration of omeprazole, a potent gastric acid suppressor, reduces the peak serum concentrations of itraconazole oral. Significance: Our data suggests that caution should be taken when administering omeprazole and itraconazole oral solution concurrently. In addition, adequate absorption of itraconazole oral solution in persons with documented gastric hypoacidity remains to be demonstrated. Therefore, documentation of adequate serum itraconazole concentrations may be important to achieving therapeutic success in those with compromised gastric acidity. Future Plans: We plan to complete the study in the remaining two patients who have already enrolled, and then analyze HPLC results for all 17 patients. Results of this study will be submitted for publication in a peer-review journal in 1999.
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