PROLONGED, BUT NOT DIMINISHED, ZIDOVUDINE ABSORPTION INDUCED BY A HIGH-FAT BREAKFAST

Study Objective. To determine the effect of a high-fat breakfast on si ngle-dose, zidovudine (ZDV) pharmacokinetics. Design. Open-label, rand omized, 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 sin gle 100-mg oral doses of ZDV as follows: after an 8-hour fast (treatme nt A), with a high-fat breakfast (treatment B), and 3 hours after a hi gh-fat breakfast (treatment C). Measurements and Main Results. The hig h-fat breakfast significantly reduced the mean (coefficient of variati on) maximum plasma concentration (C(max)) from 806 (55%) ng/ml with tr eatment A to 341 (47%) and 424 (42%) ng/ml with treatments B and C, re spectively. 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 trea tments B and C, respectively. Area under the plasma ZDV concentration- time curve (AUC) was not statistically different across the study trea tments. 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 absorptio n was prolonged and C(max) was reduced relative to fasting. However, s ystemic exposure, as indicated by AUC, was unchanged.