Combination pharmacokinetics and pharmacodynamics of dihydroartemisinin-piperaquine and primaquine in patients with uncomplicated falciparum malaria in halmahera Indonesia

Malaria remains one of the deadly diseases in Indonesia. In its attempts to cure malaria, the government has implemented the DHP formulation (dihydroartemisinin-piperaquine) added with primaquine. However, no study has been carried out on the pharmacokinetics and pharmacodynamics of this combination. The purpose of this research is to compare absorption rate constant (Ka), time of maximum concentration observed (Tmax), elimination half-life (t1/2), volume of distribution (VD), clearance (CL), plasma maximum concentration (Cmax), and area under curve (AUC) of the DHA-piperaquine (DHP) and primaquine combination in 12 uncomplicated falciparum malaria patients and the pharmacological effects. Random clinical tests were conducted with an experimental method to 12 patients from September to December 2014. Blood samples were taken sequentially, starting from day 0 to day 28, and then tested using LC-MS to measure the kinetic concentration. The results showed that the kinetic profile of DHA, piperaquine, and primaquine synergized well with no contradictions recorded as the patients were cured without any side effects. The DHP-primaquine combination (Cmax and Auc) was able to clean the parasite in just two days of treatment and showed that there was a significant relation (P = 0.001 < 0.05 AND 0.010 < 0.05) between the drug content and parasite clearance. The pharmacological effect was APCR, with 100% of treatment success.