ObjectiveTo evaluate the pharmacokinetics of α- and β-diastereomers of arteether in healthy male volunteers.Participants and methodsThe study was a single-centre clinical pharmacokinetic trial in healthy male subjects. A group comprising 13 subjects aged 25–50 years received a single intramuscular 150mg individual dose of the arteether formulation containing α- and β-isomers in a 30 : 70 ratio. Serial blood samples collected over a period of 0–192 hours were analysed by high-performance liquid chromatography-electrospray ionisation/tandem mass spectrometry and the plasma concentrations were subjected to compartmental and noncompartmental analyses. Pharmacodynamic parameters such as area under the inhibitory curve, ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC), maximum plasma concentration to MIC (Cmax/MIC) and time that plasma concentration exceeds the MIC (T>MIC) were calculatedin vitroin four strains ofPlasmodium falciparumto evaluate thein vivoeffectiveness of the proposed dosage regimen.ResultsThere were no adverse effects observed during the study. The extent of metabolism of arteether to dihydroartemisinin (DHA) was low (~5%) so as to be therapeutically nonsignificant. The pharmacokinetic profiles of the arteether diastereomers were different, and the maximum plasma concentrations of α- and β-isomers were reached at 4.77 ± 1.21 hours and 6.96 ± 1.62 hours, respectively, after which they showed biphasic decline with apparent terminal elimination half-lives of 13.24 ± 1.08 hours and 30.17 ± 2.44 hours, respectively. The plasma and renal clearances, as well as whole blood to plasma partition ratios of the isomers, were comparable, while the apparent volume of distribution during terminal phase of the β-isomer was approximately 3-fold higher than that of the α-isomer.In vitroerythrocyte culture experiments with four strains ofP. falciparumshowed similar MICs for both isomers of arteether. The highest observed MIC of 8 μg/L was selected for estimating the pharmacokinetic and pharmacodynamic parameters, which showed excellent correlation with published data on the clinical efficacy of arteether.ConclusionThe pharmacokinetics of arteether isomers demonstrated stereoselectivity, which was reflected mainly in the volume of distribution and the terminal elimination half-life. The α- and β-isomers of arteether appeared to compliment each other pharmacokinetically, with the α-isomer providing comparatively rapid and higher plasma concentrations resulting in immediate reduction in percentage parasitaemia, while the β-isomer, with its longer terminal elimination half-life, mean residence time and sustained plasma concentrations, maintained the activity for longer periods. The extent of metabolic conversion of arteether to DHA was minimal, so as to have any therapeutic or toxic significance.