Bioequivalence Assessment of Five Brands of Antimalarial Drugs Marketed in Rivers State Using Statistical Tool

Abstract

Malaria remains a major public health challenge in Sub-Saharan Africa, with artemether-lumefantrine (AL) as the first-line treatment for uncomplicated Plasmodium falciparum malaria. Ensuring bioequivalence among generic AL brands is crucial for therapeutic interchangeability and effective malaria control. This study evaluated the bioequivalence of four generic antimalarial brands (Drugs A, B, C, D) against a standard AL formulation using clinical recovery time as the primary endpoint in 80 malaria patients. An Indirect Assay Design (IAD) was employed, administering five antimalarial drug brands randomly to malaria patients. The primary outcome was time to clinical recovery (in hours) following completion of treatment. Bioequivalence was assessed using ANOVA and Logistic 4-parameter equivalence tests in JMP software version 17.

Equivalence was declared when 90% confidence intervals for key parameters (growth rate, inflection point, lower/upper asymptotes) fell within predefined decision limits. Parameter estimates revealed Drug A was bioequivalent to Drug C shown in parameter estimate: -4.33; SE: 2.102; tRatio: -2.06; p=0.042). Equivalence testing confirmed Drugs A and C had comparable potency profiles: growth rate ratio (2.4:0.15), inflection point (1.3:0.65), lower asymptote (1.2:0.75), and upper asymptote (1.1:0.85). Drugs B and D failed equivalence criteria, indicating potential formulation differences affecting clinical efficacy. Drugs A demonstrated statistical bioequivalence to Drug C based on recovery time analysis, ANOVA and Logistic 4-parameter equivalence tests. These findings support their therapeutic interchangeability for uncomplicated malaria treatment. Drugs B and D require further quality assessment. This study validates the use of clinical recovery time as a practical bioequivalence endpoint in resource-limited settings where pharmacokinetic studies are challenging.