• Effect of Food on Oral Bioavailability of Didanosine from Delayed Release Capsules Containing Enteric Coated Beads
  Abstract 499
  Authored by B. D. Damle, J.-H. Yan, D. Behr, E. O'mara, P. Nichola, S. Kaul, C. A. Knupp, (Bristol-Myers Squibb, Princeton, NJ)
  View the original abstract

Clinicians who treat HIV-infected patients and use didanosine (Videx) or didanosine from encapsulated enteric coated beads (Videx EC) are well aware of the general instruction that Videx and Videx EC are to be taken on an empty stomach. The significance and importance of this instruction in achieving adequate drug levels, at least as far as Videx EC is concerned, has never been fully clarified. Four studies presented at the 41st ICAAC that were designed to assess the effect of food and timing of meals on the bioavailability of Videx EC provided a significant amount of information that helps to clarify this important issue.

The four studies involved a total of 334 patients and were open-label, single-dose, randomized, cross-over studies conducted in healthy subjects. In these studies, 400mg of Videx EC was given concomitantly with a high fat meal (757 calories), light meal (373 calories), yogurt (69 calories), or apple sauce (25 calories). In two of these studies Videx EC was given at various dosing intervals before and after a light meal.

The high-fat meal, light meal, yogurt, and apple sauce decreased the Cmax of Videx EC by 46%, 22%, 30%, and 24%, respectively, and lowered the AUC by 19%, 27%, 20%, and 18%, respectively.

If the Videx EC was given one hour before a meal, Cmax and AUC were lower by 15% and 24%, respectively, and for two hours after a meal, were lower by 15% and 10%, respectively. For one and a half, two, and three hours before meals, Cmax values were unchanged but AUC was lower by 10%, 4%, and 0%, respectively. There were no deaths or serious adverse events in the studies.

These data indicate that the Cmax and AUC of Videx EC are reduced by taking it with food, but that some of the food effects were relatively mild. These data do not do anything to change the general recommendation that Videx EC be taken on an empty stomach, and it appears that taking Videx EC at least one and a half hours before or two hours after a meal are sufficient to achieve Videx EC concentrations equivalent to those achieved with fasting. These data do give rise to some interesting pharmacologic interaction questions, especially since some drugs, notably tenofovir (Viread), can significantly elevate Videx EC levels and have the potential to correct the relatively mild decreases in Videx that occur with a light meal, yogurt or apple sauce.