[WeOa0206] Significantly reduced food effect and pharmacokinetic variability with a novel lopinavir/ritonavir tablet formulation

3rd International AIDS Society Conference on HIV Pathogenesis and Treatment

Rio de Janeiro - July 24 - 27, 2005

SIGNIFICANTLY REDUCED FOOD EFFECT AND PHARMACOKINETIC VARIABILITY WITH A NOVEL LOPINAVIR/RITONAVIR TABLET FORMULATION

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. WeOa0206

Awni W., Chiu Y.-L., Zhu T., Braun N., Klein C., Heuser R., Breitenbach J., Morris J., Doan T., Brun S., Hanna G.
Abbott Laboratories, Abbott Park, IL, United States of America

INTRODUCTION: Lopinavir/ritonavir is currently available as a 133/33 mg soft gel capsule (SGC) that requires refrigeration and administration of 6 pills/day with meals to maximize lopinavir bioavailability. A novel melt-extrusion (Meltrex™) 200/50 mg tablet formulation was developed that reduces daily pill count to 4 pills/day and requires no refrigeration.

METHODS: The tablet formulation was assessed in 3 studies with a total of 141 healthy adult subjects to compare the pharmacokinetics of lopinavir and ritonavir after single or multiple doses and under different meal conditions (fasting, moderate-fat and high-fat meal) to the SGC. Pharmacokinetic parameters, including area under the plasma concentration time curve (AUC) and maximum concentration (C_max), of lopinavir and ritonavir were estimated using standard non-compartmental methods. Bioequivalence was assessed under moderate-fat meal conditions.

RESULTS: The tablet met bioequivalence criteria with respect to lopinavir and ritonavir AUC relative to the SGC under the reference moderate-fat meal conditions. Compared to administration of the tablet under fasting conditions, the AUC of lopinavir and ritonavir increased by 19% and 4% following a high-fat meal, and 27% and 15% following a moderate-fat meal. The pharmacokinetics of lopinavir and ritonavir from the tablet formulation under all meal conditions were similar to the SGC under reference moderate-fat meal conditions. Variability of AUC and C_max values for lopinavir and ritonavir was significantly reduced with the tablet compared to the SGC under each meal condition, with fewer subjects experiencing extreme high or low values with the tablet. The tablet formulation was safe and well tolerated with single- and multiple-dose administrations.

CONCLUSIONS: Lopinavir and ritonavir levels were similar between tablet and SGC formulations under reference meal conditions. There was considerably less food effect with the tablet formulation, and pharmacokinetic variability was significantly reduced under all meal conditions compared to the SGC.

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Basic | WeOa0206 | George Hanna
Antiretroviral treatment strategies

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