Effect of Food on the Oral Bioavailability of Didanosine from Encapsulated Enteric-Coated Beads

• Published in: Journal of clinical pharmacology 2002-04, Vol.42 (4), p.419-427
• Main Authors: Damle, Bharat D, Yan, Jing-He, Behr, Douglas, OʼMara, Edward, Nichola, Peter, Kaul, Sanjeev, Knupp, Catherine
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - blood; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Area Under Curve; Biological and medical sciences; Biological Availability; Confidence Intervals; Cross-Over Studies; Didanosine - administration & dosage; Didanosine - adverse effects; Didanosine - blood; Dietary Fats - blood; Fasting - blood; Female; Food-Drug Interactions - physiology; Humans; Male; Medical sciences; Microspheres; Pharmacology. Drug treatments; Tablets, Enteric-Coated
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270002424008

The objective of this study was to assess the effect of food and timing of meals on the bioavailability of didanosine from encapsulated enteric-coated beads. Four different independent, open-label, single-dose, randomized, crossover studies were conducted in healthy subjects (n = 20–30). Didanosine (400 mg) was given concomitantly with a high-fat meal, light meal, yogurt, and applesauce. In addition, didanosine was given 1, 1.5, 2, and 3 hours before and 2 hours after a light meal. Statistical comparison with fasting conditions was made using the equivalence approach for Cmax (70%-143%) and AUC (80%-125%). The high-fat meal, light meal, yogurt, and applesauce decreased the Cmax by 46%, 22%, 30%, and 24%, respectively, and lowered the AUC by 19%, 27%, 20%, and 18%, respectively; statistical analyses indicated an indeterminate food effect, except for the Cmax for the high-fat meal. For 1 hour before meal, Cmax and AUC were lower by 15% and 24% and, for 2 hours after meal, were lower by 15% and 10%, respectively. There was an indeterminate food effect for 1 hour before the meal treatment; in addition, 2 hours after the meal, treatment approached statistical equivalence, missing narrowly on the lower bounds. For 1.5, 2, and 3 hours before meal treatments, Cmax values were unchanged, but AUC was lower by 10%, 4%, and 0%, respectively; lack of food effect was observed for all three treatments. Across studies, median time to Cmax ranged from 1.67 to 2.67 hours but was delayed by 2.5 to 3 hours with high-fat and light meals compared to fasting conditions. The half-life of didanosine was 1.5 to 2 hours. It was concluded that the bioavailability of didanosine from encapsulated enteric-coated beads was reduced by approximately 20% to 25% with food, which can be circumvented by taking didanosine on an empty stomach. The clinical significance of such moderate reductions in didanosine exposure with food, especially as part of a highly active antiretroviral therapy, is not clear.