Examining the Research Gap in Population Pharmacokinetics of Antimalarials in Nigerian Paediatric Patients

Population pharmacokinetic data for antimalarial drugs in Nigerian paediatric patients are critically insufficient, creating dosing uncertainty and potentially contributing to treatment failure and resistance. This study examined the extent of the existing research gap and developed a protocol for a population pharmacokinetic study of artemether-lumefantrine in Nigerian children under twelve years of age. A systematic scoping review and protocol development methodology was employed. The scoping review searched four databases for population pharmacokinetic studies of antimalarials in African paediatric populations, identifying 28 eligible studies. Analysis revealed that Nigerian paediatric populations were represented in only two studies, and no study had specifically sampled children from all major ecological zones of Nigeria, where genetic, nutritional, and co-infection variability may significantly influence drug disposition. Key pharmacokinetic determinants including CYP3A4 and CYP2C8 polymorphisms, nutritional status, malaria severity, and age-related maturation were not consistently accounted for in available models. The developed protocol for a multi-centre population pharmacokinetic study encompasses sampling design across five health zones, sparse sampling optimisation, nonlinear mixed effects modelling using NONMEM, and covariate analysis incorporating genetic and nutritional variables. Expert review by eight pharmacokineticians and paediatric pharmacologists confirmed the scientific rigour of the protocol. The study provides the most comprehensive analysis of the Nigerian paediatric antimalarial pharmacokinetics research gap to date and a validated study protocol for future funding applications.

Keywords: population pharmacokinetics, antimalarials, paediatric patients, Nigeria, artemether-lumefantrine