Prolonged, But Not Diminished, Zidovudine Absorption Induced by a High‐Fat Breakfast

STUDY OBJECTIVE: To determine the effect of a high-fat breakfast on single-dose, zidovudine (ZDV) pharmacokinetics. DESIGN: Open-label, randomized, crossover study. PATIENTS: Eighteen asymptomatic subjects (12 men, 6 women) infected with the human immunodeficiency virus (mean CD4 cell counts of 512 +/- 178/mm3). INTERVENTIONS: Subjects received single 100-mg oral doses of ZDV as follows: after an 8-hour fast (treatment A), with a high-fat breakfast (treatment B), and 3 hours after a high-fat breakfast (treatment C). MEASUREMENTS AND MAIN RESULTS: The high-fat breakfast significantly reduced the mean (coefficient of variation) maximum plasma concentration (Cmax) from 806 (55%) ng/ml with treatment A to 341 (47%) and 424 (42%) ng/ml with treatments B and C, respectively. The time to Cmax was significantly prolonged from 0.68 (30%) hours with treatment A to 1.7 (54%) and 1.3 (42%) hours with treatments B and C, respectively. Area under the plasma ZDV concentration-time curve (AUC) was not statistically different across the study treatments. Men had significantly lower (35%) renal clearances of both ZDV and its glucuronide metabolite than women. CONCLUSIONS: When ZDV was given either with or 3 hours after a high-fat breakfast, its absorption was prolonged and Cmax was reduced relative to fasting. However, systemic exposure, as indicated by AUC, was unchanged.