Comparative Pharmacokinetics of Generic versus Innovator Artemether-Lumefantrine Formulations in Healthy Volunteers: A Bioequivalence Study in Nigeria

Background: The proliferation of generic artemether-lumefantrine (AL) formulations in the Nigerian market raises important concerns about bioequivalence, therapeutic consistency, and the risk of treatment failure. While regulatory bioequivalence standards exist, post-market pharmacokinetic data from Nigerian populations are scarce. This study compared the pharmacokinetics of a domestically produced generic AL formulation with the innovator Coartem in healthy Nigerian volunteers. Methods: A two-period crossover bioequivalence study was conducted in 24 healthy adult volunteers with a four-week washout period. Blood samples were collected at 14 time points over 72 hours following single-dose administration. Plasma drug concentrations were measured by validated HPLC-MS/MS. Primary pharmacokinetic parameters including AUC0-t, AUC0-inf, Cmax, and Tmax were calculated using non-compartmental analysis. Results: The 90 percent confidence intervals for AUC and Cmax ratios between generic and innovator formulations fell within the 80 to 125 percent bioequivalence window for artemether but showed marginal deviation for lumefantrine Cmax (lower CI: 76.4%). Tmax was comparable between formulations. No serious adverse events were recorded. Conclusion: The tested generic AL formulation demonstrated bioequivalence for artemether but borderline for lumefantrine, warranting further investigation before broad therapeutic substitution. Strengthened regulatory post-market surveillance is recommended. Keywords: artemether-lumefantrine, bioequivalence, pharmacokinetics, generic drugs, malaria treatment