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 (C_max) 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 C_max 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 C_max was reduced relative to fasting. However, systemic exposure, as indicated by AUC, was unchanged. (Pharmacotherapy 1994;14(6):671–677) 1994 Pharmacotherapy Publications Inc.