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Prolonged, But Not Diminished, Zidovudine Absorption Induced by a High‐Fat Breakfast
Author(s) -
Shelton Mark J.,
Portmore Amy,
Blum M. Robert,
Sadler Brian M.,
Reichman Richard C.,
Morse Gene D.
Publication year - 1994
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1994.tb04159.x
Subject(s) - zidovudine , pharmacokinetics , crossover study , medicine , asymptomatic , metabolite , coefficient of variation , human immunodeficiency virus (hiv) , chemistry , immunology , viral disease , placebo , alternative medicine , pathology , chromatography
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/mm 3 ). 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)