Pilot study: bioequivalence of dihydroartemisinin in dihydroartemisinin-piperaquine tablet generic formulation in healthy Indonesian volunteers

Bioequivalence test should be carried out for copy medicine, including dihydroartemisinin-piperaquine (DHP), which is used to treat critical diseases requiring medication. To predict the bioequivalence of film coated DHP generic tablets compared to the reference, a randomized controlled trial, single blind, single dose cross over design, two sequences, 2 periods, and wash-out period 7 days was conducted on 8 healthy adults. Blood samples were taken at certain times; plasma levels of dihydroartemisinin (DHA) were determined and analyzed for pharmacokinetics profile using UPLC MS MS system. The mean +/- SD of AUC0-24, Cmax, Tmax, and T1/2 of the test drug (T) in the following order were 220.07 +/- 64.48 ng.mL-1.hour; 119.00 +/- 37.66 ng.mL-1.hour; 1.16 +/- 0.30 hour; and 1.06 +/- 0.31 hour. The mean +/- SD of AUC0-24, Cmax, Tmax, and T1/2 of the reference drug (R) were 301.91 +/- 161.30 ng.mL-1.hour; 203.60 +/- 91.04 ng.mL-1.hour; 0.94 +/- 0.35 hour; and 0.80 +/- 0.21 hour. Based on statistical analysis, the geometrics mean ratio (T/R) for the Cmax and AUC0-t were 0.6083 with 90% CI (0.4853-0.7624) and 0.7769 with 90% CI (0.6493-0.9295) respectively. Kinetic profiles between the two products were the same, however the test drug is relatively inferior compared to the reference drug.