Bioequivalence study of lumefantrine rectal enema and the commercially available generic oral suspension. A pilot study

Abstract

Children under five years of age, with severe or cerebral malaria, cannot consume oral medication especially if they are vomiting or are unconscious. In such situations they are given an injectable drug until they can tolerate oral medication. The situation is bad in Sub-Saharan Africa, especially in rural areas as children are sometimes referred to the closest referral health care facility for proper management. The aim of this study was therefore to conduct a pilot study to estimate the bioavailability of lumefantrine (LF) when administered as a rectal enema, and compare it with a commercially available oral suspension, in rabbits. The study was conducted on six healthy rabbits in an open randomized, crossover three sequence, single dose study, where each rabbit received rectal and oral formulations. The oral formulation was administered under fed and fasted conditions. A two-week washout period was allowed between the experiments. LF was quantified in rabbit plasma using ultraperformance liquid chromatography tandem mass spectrometry (UPLC MS/MS). Results showed that the relative bioavailability of rectal LF was about four times higher than oral. The observed data suggest that a significant adjustment in the dose will be required when LF is administered via the rectal route. The data provide important information for the next step in finding a method to provide a rescue treatment for children with severe or cerebral malaria.