3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

PHARMACOKINETIC INTERACTION BETWEEN ATAZANAVIR AND OMEPRAZOLE IN HEALTHY SUBJECTS

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. WePe3.3C08

Agarwala S., Gray K., Eley T., Wang Y., Hughes E., Grasela D.
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, United States of America

INTRODUCTION: Atazanavir (ATV), a potent, once-daily PI, has been extensively studied, including Phase III trials of naïve patients versus a standard of care regimen containing efavirenz and treatment-experienced patients versus a standard of care regimen containing lopinavir/RTV. ATV exhibits pH-dependent solubility; ATV bioavailability may decrease at higher pH. Proton pump inhibitors such as OMP increase gastric pH. The objectives were to evaluate the effect of (1) OMP on the PK of ATV, (2) ATV on the PK of OMP as a CYP2C19 probe.

METHODS: An open label study with OMP 40mg was conducted. Healthy subjects (n=48) received ATV 400 (A) for 6d. Following randomization into three treatments (n=16), subjects received ATV 400+OMP QD for 6d (B); ATV 400+OMP QD + cola for 6d (C); or ATV/RTV 300/100+OMP QD for 10d (D). ATV or ATV/RTV were administered with a light meal; OMP was administered fasted 2h before ATV/RTV. For CYP2C19 probe analysis, subjects in Treatment B received ATV 400, 2h before OMP on the first day of dosing only and also received a single-dose of OMP (E) following a washout. Blood samples were collected for PK.

RESULTS: Ratios of geometric means (90% C.I.) for ATV and OMP PK are below.

Cola did not mitigate the reduction in ATV exposures by OMP. No new/unexpected adverse effects attributed to study drugs were noted.

CONCLUSIONS: PPIs should not be used with ATV for the regimens studied. The 43% increase in OMP AUC by ATV does not suggest clinically significant CYP2C19 inhibition by ATV, since the AUC of OMP in CYP2C19 poor metabolizers is increased by approximately 5-fold.

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050724
Clinical | WePe3.3C08 | Sangeeta Agarwala
Drug Interactions

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