Lack of food effect with Meltrex formulation of lopinavir/r

10 June 2006. Related: Conference reports, Antiretrovirals, PK Workshop 7th 2006.

Simon Collins, HIV i-Base

Chiu and colleagues from Abbott laboratories presented two posters comparing food effect and drug level variability of the new Meltrex formulation of lopinavir/r (Kaletra) compared to the original soft gel capsule formulation. [1]

In a crossover study, in 46 HIV-negative adult volunteers received single doses of lopinavir/ritonavir 400/100 mg as tablet (test, T) or SGC (reference, R) under moderate-fat meal conditions, separated by washout periods of >/= 5 days. Drug sequences were randomly assigned to TTR and RTT in three crossover periods. A linear effects model was used to estimated lopinavir and ritonavir PK area under the plasma concentration time curve (AUC), Cmax) and concentration at 12 hours post-dose (C12). The total variance, detailed in Table 1, was calculated as the sum of the within- and between-subject variances.

Table 1: Inter- and intra-patient variability between SGC and Meltrex formulations of lopinavir/r

Between-patient variability

Within-patient variability

The researchers concluded that the Meltrex formulation of lopinavir/r provides more consistent PK performance within, and between, subjects compared to the soft gel capsule.

A second poster at the Workshop presented data on the lack of a food effect with the new Meltrex formulation of lopinavir/r. [2] Lopinavir/ritonavir soft gelatin capsule (SGC) and oral solution formulations must be administered under fed conditions in order to maximize bioavailability of lopinavir. Compared to fasting, the bioavailability under moderate-fat and high-fat meal conditions increased by 56% and 96%, respectively, for the SGC formulation.

In this study, 107 healthy subjects in 2 randomised, open-label studies received single doses of lopinavir/ritonavir 400/100 mg SGC and tablet formulations in a crossover fashion under three different controlled meal conditions: fasting, moderate- and high-fat meals. Results were compared to the SGC under the moderate-fat meal condition and bioequivalence AUC criteria were met because the 90% CIs were contained entirely within the 0.8-1.25 range.

The authors concluded that the tablet formulation under different meal conditions resulted in lopinavir average concentrations and maximum exposures similar to the approved SGC reference regimen, and that the Meltrex tablet formulation may be taken without regard to food.

Comment

These studies were performed in HIV negative volunteers. As yet, there is no data from the Meltrex formulation in HIV-positive patients.

References:

1. Chiu YL et al. Assessment of pharmacokinetic variability for lopinavir/ritonavir (LPV/r) tablet and soft-gel capsule (SGC) formulations. 7th International Workshop on Clinical Pharmacology of HIV Therapy, 20-22 April 2006, Lisbon. Abstract 78-A.
2. Chiu YL et al. Lack of food effect on the bioavailability of lopinavir/ritonavir tablet formulation. 7th Intl Workshop on Clinical PK of HIV Therapy, 20-22 April 2006, Lisbon. Abs 78-B