Pharmacokinetics of a Five-day Oral Dihydroartemisinin Monotherapy Regimen in Patients with Uncomplicated Falciparum Malaria

Summary:The pharmacokinetics of dihydroartemisinin (DHA) in a 5-day oral monotherapy regimen was investigated in ten adult Vietnamese patients with uncomplicated falciparum malaria. The patients were treated with a total dose of 900 mg DHA divided as single daily doses of 300, 300, 100, 100, and 100 mg from day 0 through day 4. There were no differences in the concentrations of DHA within the first two days of treatment. The pharmacokinetics of DHA in the acute phase, however, was significantly different from that in the convalescent phase of malaria. Reduced half-life (T1/2z) and lower area under concentration curve (AUC∞) values were observed on the final day of treatment in comparison to those obtained on the first day. These decreases in T1/2z and AUC∞ were observed in concordance with increased drug clearance (CL/F). Furthermore, the time required to reach maximum plasma DHA concentration (Tmax) on day 4 was shorter than that on day 0. Together, these findings suggest that the change in pharmacokinetics of DHA is related to the physiological change in malaria patients between the acute and convalescent phases of the disease.