BIOAVAILABILITY AND BIOEQUIVALENCE EVALUATION OF SOME GENERIC PRODUCTS OF ARTEMETHER-LUMEFANTRINE DOUBLE STRENGTH TABLETS MARKETED IN NIGERIA

The study was aimed at evaluating the bioavailability and bioequivalence of generic products of artemether-lumefantrine (AL) antimalarial double strength oral tablet formulation. A non-randomized open label single dose study in eighteen healthy African male subjects was designed. The volunteers were administered one tablet of a product with a fatty meal and 0.5 L of water, after overnight fast. Venous blood sampling was taken at 0, 1, 2, 4, 6 and 8 h post-dose and plasma samples analyzed for artemether and lumefantrine exposure simultaneously using a validated high performance liquid chromatographic system with Chromosil C18 column, flow rate and UV detection at 1.0 mL/min and 216 nm, respectively. Acetonitrile: potassium dihydrogen phosphate (70: 30%, v/v) and nevirapine were employed as mobile phase and internal standard, respectively. The primary endpoints were area under the plasma concentration time curve (AUC) from zero to 8 h and maximum plasma concentration (Cmax). The 90% confidence interval for the ratio of the geometric means of AUC0-8 was compared with the established bioequivalence limit. All enrolled subjects with mean age 28.5 plus or minus 4.5 years completed the study. The Cmax for artemether and lumefantrine for the products ranged from 0.225 - 0.558 mu g/mL and 0.319 - 0.517 mu g/mL, respectively. Drug products AL1 and AL2 met the bioequivalence criteria. The other products failed the pharmacopoeia test specification for chemical content with respect to either or both API and their pharmacokinetic profiles varied with statistical significant differences (P>0.05). Only two of the generic products studied were bioequivalent and could be switched.