Effect of a Cola Beverage on the Bioavailability of Itraconazole in the Presence of H₂ Blockers

Abstract

Thirty-three healthy individuals participated in an open-label, randomized, three-way crossover study designed to compared the bioavailability of a single 200-mg oral dose of itraconazole when administered alone or after treatment with ranitidine, both with and without coadministration of a cola beverage. Each treatment phase was separated by a 2-week washout period. Participants pretreated with ranitidine were required to have a gastric pH of at least 6.0 before receiving itraconazole. An analysis of the area under the curve (AUC) and peak plasma concentration (Cmax) data indicated that the bioavailability of itraconazole was significantly reduced when the gastric pH was increased by pretreatment with ranitidine but showed that this effect was counteracted by the coadministration of an acidic solution (e.g., a cola beverage) that transiently reduced the gastric pH. These findings suggest that the coadministration of an acidic beverage with itraconazole may be an effective approach in improving the bioavailability of itraconazole in patients who are hypochlorhydric or who are taking gastric acid suppressants.

Co-administration of Fluoxetine Alters the Steady State Pharmacokinetics of Fluconazole after Multiple Oral Administration in Dogs

“…The acceleration of transit through the gastrointestinal tract would result in reduced absorption of drugs [19]. Drugs that increase gastric pH (e.g., H 2 antagonists and proton pump inhibitors) could slow the dissolution of the solid dosage forms of other drugs such as ketoconazole and itraconazole [11,20] and decrease drug available for absorption in the intestinal lumen. Other pharmacokinetic studies have documented 30-60% reductions in serum itraconazole concentrations (C max , AUC 0-24 ) in healthy volunteers administered itraconazole capsules with either famotidine or omeprazole [21][22][23].…”

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

“…Itraconazole is a triazole antifungal, with activity against Candida species (including some fluconazole- 53 or vitamin C drink 54 ) at low gastric pH. Oral itraconazole solution has increased bioavailability (B30-35%) compared with the capsules, but in contrast to the capsules, is maximally absorbed during fasting.…”

Soluble Itraconazole in Tablet Form Using Disordered Drug Delivery Approach: Critical Scale-up Considerations and Bio-equivalence Studies

“…We hypothesize that this bio-variable nature of itraconazole may be partly responsible for the observed anomalous behaviour. Additionally, the pharmacokinetics of orally administered itraconazole in plasma are dose dependent, and absorption from the gastrointestinal tract is affected by various factors, such as food intake versus fasting state (30,31), gastric pH (32,33), drug interactions (33,34), AIDS and the pharmaceutical formulation of the drug (35,36). As per our power calculations, we found that the % CV in the subjects for the innovator product was in excess of 35%, and as per the reported statistical calculations, the number of patients must be more than 85.…”