Impact of food administration on lopinavir-ritonavir bioequivalence studies.

ABSTRACT

A bioequivalence study in 16 Caucasian healthy volunteers (eight male, eight female), comparing plasma drug concentrations after a single oral dose of lopinavir and ritonavir (400 and 100mg, respectively), was carried out following a two-period, two-sequence, two-treatment, randomized crossover design. Formulations were given 15 min after a moderate-fat breakfast in order to diminish both the intrinsic highly-variable performance and the sex differences observed in bioequivalence trials under fasting conditions. Ninety percent confidence intervals for the Test/Reference (T/R) ratio of geometric means for area under concentration-time curve (AUC) and maximum concentration (C(MAX)), either for lopinavir or ritonavir, were within the range of 0.80-1.25. Coprandial administration of formulations not only reduced the number of subjects required for bioequivalence assessment, reducing both ethical and economic cost of the trial, but also the sex differences in the T/R ratio of means.