July 27, 2005
Fixed-dose lopinavir/ritonavir (LPV/r, Kaletra) is widely used in treatment-naive patients and, especially, in treatment-experienced patients. The high plasma concentrations of lopinavir (LPV) achieved through the ritonavir (RTV, Norvir) boosting likely account for its high potency and low risk of resistance potential. However, the currently available formulation is sometimes associated with gastrointestinal symptoms such as nausea and diarrhea. In addition, the pill burden (6 capsules daily) is relatively high compared with newer protease inhibitors such as atazanavir (ATV, Reyataz) and fosamprenavir (FPV, 908, Lexiva, Telzir). One other issue is that the capsules require refrigeration if the ambient temperature exceeds 78 degrees -- a common occurrence in the summer months and, especially, in resource-poor settings. In this presentation, researchers from Abbott pharmaceutical presented information on a new tablet formulation of lopinavir/ritonavir.
Employing a novel "melt extrusion" technology, the new formulation disperses the lopinavir and ritonavir throughout the tablet in a uniform solid, with the active ingredients dissolved in a hydrophilic polymer. Each tablet contains 200 mg of lopinavir and 50 mg of ritonavir, allowing for a 2-tablet twice-daily dosage.
In pharmacokinetic studies involving 141 healthy volunteers, the tablet formulation was rapidly absorbed, yielding slightly higher exposure to lopinavir and ritonavir than the capsules. In addition, there was a narrower range of lopinavir concentrations, with fewer patients showing very high or very low levels. Encouragingly, lopinavir levels were similar whether the tablets were dosed with or without food.
Although tolerability data were not given during this slide session, it is hoped that the removal of the excipients that are included in the capsule formulation will reduce the incidence of gastrointestinal side effects. If realized, this improved tolerability will add to the other advantages of the new formulation, which include lower pill burden, lack of food effect and room temperature storage. The U.S. Food and Drug Administration is currently reviewing lopinavir/ritonavir tablets, and will possibly approve them for use later this year.
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