Population Pharmacokinetic of Artemisinin Derivatives

. Artemisinin-based combination therapy is recommended by WHO as the first-line treatment for uncomplicated P. falciparum malaria. Physiological changes occur during pregnancy, age-related differences between adult and children that can influence medicine pharmacokinetics and pharmacodynamics. Disease state and other complications also may affect the antimalarial dispositions. This review examines artemisinin derivatives population pharmacokinetic studies conducted in various sub-populations, highlighting commonalities and variations among the studies to evaluate the variability among different sub-populations. An electronic literature search was conducted from Embase, PubMed and ScienceDirect according to the recommendations of PRISMA, using the search term Artemether and population pharmacokinetics, or Artemether and nonlinear mixed effect, or Artemether and nonlinear mixed-effects, or Artemether and NONMEM. Sixteen articles were included in this review; 4 out of which were caried out in each of children, and pregnant women. The reported PK values in pregnant/non-pregnant studies ranged from minimum of 197 and 57 to maximum of 2160 and 373 L for the V of artemisinin and DHA respectively, while in children reported as minimum of 28.2 and 11 L and maximum of 382 and 52L. Clearance of artemisinin and DHA in children ranged from minimum of 14.3 and 11 L/h and maximum of 146 and 95.2 L/h, respectively. The co-administration of efavirenz, nevirapine, or lopinavir/ritonavir decreased the exposure to dihydroartemisinin by 71.7, 41.3, and 59.7%, respectively. Many variables were evaluated, but a few ones such as bodyweight, on CL and V, concomitant antiretroviral on CL were included in final model to describe the variability between sub-populations.