EFFECT OF TIME OF FOOD ADMINISTRATION ON THE BIOAVAILABILITY OF DIDANOSINE FROM A CHEWABLE TABLET FORMULATION

The effect of the time of food administration on the bioavailability of didanosine, administered as a 300-mg dose of a chewable tablet formulation, was evaluated in 10 men seropositive for the human immunodeficiency virus (HIV), but free of any symptoms of acquired immune deficiency syndrome (AIDS). Using an open, randomized, balanced, incomplete block crossover study design, each patient received the dose of didanosine under four of the five following conditions: (1) after an overnight fast, (2) 30 minutes before a meal, (3) 1 hour before a meal, (4) 1 hour after a meal, or (5) 2 hours after a meal. The meal consisted of a standard high-fat, high-calorie breakfast, consumed over a 15-minute period. Serial blood samples and the total urinary output were collected over a 12-hour interval after each dose for analysis using validated high-pressure liquid chromatography (HPLC)/ultraviolet (UV) methods. Concentration data were used to calculate pharmacokinetic parameters using noncompartmental methods. There were no significant differences among the fasting, 30-minute before, and 1-hour before the meal treatments with respect to maximum peak plasma concentration (Cmax), area under the curve (AUC(0-infinity)), or urinary recovery (%UR). Values for Cmax, AUC(0-infinity), and %UR observed for the 1 and 2 hours after the meal treatments were significantly less than those obtained under either fasting conditions or before the meal. There were no significant differences among any of the treatments with respect to time to reach peak concentration (tmax), half-life (t1/2), or renal clearance (CL(R)). Based on the data from this study, it is recommended that didanosine be administered 30 minutes to 1 hour before a meal, but not within 2 hours after a meal.