Prolonged, but not diminished, zidovudine absorption induced by a high-fat breakfast.
OBJECTIVE
To determine the effect of a high-fat breakfast on single-dose, zidovudine (ZDV) pharmacokinetics.


METHODS
Open-label, randomized, crossover study.


METHODS
Eighteen asymptomatic subjects (12 men, 6 women) infected with the human immunodeficiency virus (mean CD4 cell counts of 512 +/- 178/mm3).


METHODS
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).


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.
Shelton
M J
MJ
Department of Pharmacy Practice, State University of New York at Buffalo.
Portmore
A
A
Blum
M R
MR
Sadler
B M
BM
Reichman
R C
RC
Morse
G D
GD
D000284:Administration, Oral; D000328:Adult; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004435:Eating; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D013997:Time Factors; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D004041:Dietary Fats; D015215:Zidovudine