Inhibition of atazanavir oral absorption by lansoprazole gastric acid suppression in healthy volunteers

Study Objective. To determine whether the pharmacokinetics of atazanavir, a protease inhibitor used to treat human immunodeficiency virus (HIV) infection, are altered by its coadministration with lansoprazole, a proton pump inhibitor. Design. Single-dose, open-label, complete-crossover study. Setting. Clinical research center. Subjects. Ten healthy adult volunteers. Measurements and Main Results. In phase A, subjects received a single oral dose of atazanavir 400 mg alone. In phase B, the same subjects received oral lansoprazole 60 mg, and after 24 hours they were given a second dose of oral lansoprazole 60 mg with atazanavir 400 mg. Eleven blood samples were collected from each subject over a 24-hour period for determination of atazanavir plasma concentrations by a validated high-performance liquid chromatography assay. Pharmacokinetic analysis was performed by standard noncompartmental methods. Nine subjects completed the study, and no significant adverse events were reported. Absorption of atazanavir was significantly reduced when it was coadministered with lansoprazole, as evidenced by a 94% decline in mean area under the concentration-time curve during the 24 hours after administration (AUC _0-24)(p<0.01). The mean ± SD AUC_0-24 for phase A was 16.3 ± 9.0 μM ⊙ hour versus 0.95 ± 1.8 μM ⊙ for phase B (p<0.01). The mean ± SD maximum concentration of atazanavir was 3.2 ± 1.7 μM for phase A and 0.13 ± 0.19 μM for phase B (p<0.01). Conclusion. Acid suppression markedly reduced the bioavailability of atazanavir in this group of healthy volunteers. Based on these results, atazanavir should not be coadministered with lansoprazole or other proton pump inhibitors.