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The Effect of Food Intake on Reyataz Blood Levels
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11th International Workshop on Clinical Pharmacology and HIV Therapy, April 7-9, 2010, Sorrento
Mark Mascolini
Confirming advice that atazanavir should be taken with food, a study of 12 HIV-infected people at the Ottawa Hospital found a 53% lower 24-hour (trough) concentration of this protease inhibitor when taken with ritonavir but without food rather than with a meal[1]. Atazanavir area under the curve (AUC) was 41% lower without food than with food, and maximum concentration (Cmax) was 32% lower without food.
This study by Charles la Porte and colleagues involved 12 HIV-infected adults taking 300/100 mg of atazanavir/ritonavir once daily plus two nucleosides. Everyone had at least two consecutive viral loads below 50 copies. The investigators excluded people taking antibiotics, acid-reducing agents, illicit drugs, or natural products like St. John's wort that may affect atazanavir concentrations.
Everyone took atazanavir with food for 4 days, then half switched to taking atazanavir after a 10-hour fast for 3 days. On day 7 the investigators collected blood samples before dosing and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 hours after dosing. Then fed patients switched to the fasting routine and fasting patients switched to the fed routine and gave samples for atazanavir determinations after another 7 days.
All study participants were men and 11 were white. Their age averaged 48 years (+/- 8.6 standard deviation), height 1.72 m (+/- 0.04), weight 81.9 kg (+/- 20.7), body mass index 27.5 kg/m(2) (+/- 6.4), and CD4 count 528 (+/- 355).
Geometric mean ratios (GMR) for atazanavir AUC, Cmax, and 24-hour concentration (C24) were all substantially lower without food:
· AUC: 41% lower without food--GMR 0.59, 90% confidence interval (CI) 0.42 to 0.84
· Cmax: 32% lower without food-- GMR 0.68, 90% CI 0.45 to 1.02
· C24: 53% lower without food--GMR 0.47, 90% CI 0.31 to 0.71
Atazanavir clearance was significantly faster without food than with food (mean 17.9 versus 8.6 L/h, P = 0.003). Time to maximum concentration and half-life were similar with and without food.
Ritonavir GMR for Cmax was equivalent with and without food, but AUC was 26% lower without food (GMR 0.74, 90% CI 0.58 to 0.94) and C24 was 53% lower without food (GMR 0.47, 90% CI 0.31 to 0.70).
The impact of fasting on atazanavir levels was consistent in all study participants, but only 1 person had a 24-hour atazanavir concentration below 0.15 mg/L, the recommended cutoff to keep HIV in check. Everyone maintained virologic suppression after the study.
The Ottawa team noted that the impact of fasting on concentrations of boosted atazanavir was similar to the impact of taking atazanavir without ritonavir. US prescribing information calls for atazanavir dosing with food regardless of ritonavir boosting.
Reference
1. Giguere P, Burry J, Beique L, Zhang G, Angel J, la Porte C. The effect of food on the pharmacokinetics of atazanavir/ritonavir 300/100 mg daily in HIV-infected patients. 11th International Workshop on Clinical Pharmacology and HIV Therapy. April 7-9, 2010. Sorrento. Abstract 30.
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