Improvements in Lopinavir/Ritonavir Formulation

By Brian Boyle, MD

Lopinavir/ritonavir (Kaletra) is currently available as a 133/33 mg soft gel capsule (SGC).  While the SGC has been popular, and is the only protease inhibitor listed as preferred under the DHHS HIV treatment guidelines, it has a number of shortcomings.

The shortcomings include high pill burden (especially relative to other boosted-PI choices), the need to be taken with meals to maximize lopinavir bioavailability, and the need for refrigeration prior to distribution.

In an effort to overcome these problems, a new lopinavir/ritonavir formulation has been developed which uses a novel melt-extrusion technology (Meltrex). This new formulation of lopinavir/ritonavir is a 200/50 mg tablet that reduces daily pill count to 4 pills/day and requires no refrigeration. Data presented at the 3^rd IAS Conference in Rio de Janeiro indicates that this new formulation can be taken without regard to food and decreases inter-patient variability.

In 3 studies, that enrolled a total of 141 healthy adult subjects, the pharmacokinetics of the SGC and Meltrex tablet formulations of lopinavir/ritonavir were compared. The lopinavir and ritonavir levels achieved with the Meltrex tablet were bioequivalent to those achieved with the SGC under moderate-fat meal conditions.

Further, the Meltrex tablet formulation had significantly less variability with meals, with, compared to fasting conditions, lopinavir and ritonavir increasing, respectively,  19% and 4% following a high-fat meal, and 27% and 15% following a moderate-fat meal, and lopinavir and ritonavir levels with the Meltrex tablet under all meal conditions remaining similar to the SGC given with a moderate-fat meal.

Finally, the variability of area under the curve (AUC) and peak (Cmax) values for lopinavir and ritonavir were significantly reduced with the Meltrex tablet compared to the SGC under each meal condition, with fewer subjects experiencing extreme high or low values with the tablet.

The authors conclude, “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.”

08/10/05

Reference
W Awni and others. Significantly reduced food effect and pharmacokinetic variability with a novel lopinavir/ritonavir tablet formulation. Abstract WeOa0206 (poster). 3^rd International AIDS Society Conference on HIV Pathogenesis and Treatment. July 24-27, 2005. Rio de Janeiro, Brazil.