EFFECT OF FOOD ON THE BIOAVAILABILITY OF STAVUDINE IN SUBJECTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

A randomized, three-way crossover study was carried out to determine t he effects of food ingestion on the pharmacokinetics of stavudine (d4T ). Fifteen subjects with human immunodeficiency virus (HIV) infection and CD4(+) cell counts of greater than or equal to 200/mu l received 7 0 mg of d4T in a fasting state or 1 h before or 5 min after a standard ized high-fat breakfast. A 7- to 15-day washout period was included be tween treatments; Blood and urine were collected before and for 10 h a fter dosing, and plasma and urine d4T concentrations were determined w ith a validated radioimmunoassay. Plasma drug concentration-time data were analyzed with a noncompartmental model. The mean maximum plasma d rug concentration (C-max) and the time to C-max (T-max) for administra tion of d4T after a meal were significantly lower and longer (P = 0.00 01 for both measures) than those observed in the fasting state, althou gh the area under the concentration-time curve from time zero to infin ity (AUC(0-infinity)) was not significantly different. Neither of thes e parameters was significantly altered when d4T was taken 1 h before a meal. The bioavailability of d4T taken after a meal was 95% of that o bserved in the fasting state, and it was 97% when d4T was administered before a meal (P > 0.05 for both comparisons with the fasting state). The results of this study indicate that (i) ingestion of food does no t affect the bioavailability of d4T and that patients with HIV infecti on can take it without regard to meals, and (ii) absorption is essenti ally complete within 1 h when d4T is administered in the fasted state.