MULTIPLE-DOSE PHARMACOKINETICS OF ORAL ARTEMISININ AND COMPARISON OF ITS EFFICACY WITH THAT OF ORAL ARTESUNATE IN FALCIPARUM-MALARIA PATIENTS

The study compared the clinical efficacy and safety of oral artemisini n and oral artesunate as well as artemisinin pharmacokinetics during a nd after resolution of falciparum malaria. Forty adults with symptomat ic falciparum malaria were allocated at random to treatment with eithe r oral artemisinin (500 mg single dose on day 1 followed by 250 mg twi ce daily for 4 d and then another 500 mg single dose on day 6) or with oral artesunate (100 mg single dose on day 1 followed by 50 mg twice daily for 5 d). Patients were admitted to hospital at the Kibaha Desig nated District Hospital, Kibaha, Tanzania for the duration of treatmen t. The patients were seen once weekly for 3 more weeks. The time to pa rasite clearance (PCT) after oral artesunate (26.4+/-3.6 h) was shorte r (P=0.002) than after artemisinin (31+/-3.6 h). The fever subsidence time (FST) after oral artesunate (18.9+/-4.0 h) was also shorter (P=0. 04) than after artemisinin (21.8+/-4.6 h). Parasites were detected in 4 (20%) and 7 (35%) patients after completing treatment with artesunat e and artemisinin respectively. In these patients the parasitaemia rea ppeared at the 3rd or 4th week of follow-up. Standard haematology, blo od biochemistry and urinanalysis, performed before drug intake and aga in on days 6 and 14, were normal. No clinical abnormality was observed during the study period. Artemisinin plasma concentrations, determine d by high performance liquid chromatography with post-column derivatiz ation and detection by ultraviolet light, were followed up to 8 h afte r drug administration on days 1 and 6. Artemisinin absorption was rapi d, the maximum plasma concentrations (C-max) being attained at about 3 h. Artemisinin areas under the plasma concentration-time curve (AUG) and the C-max values were about 6 times higher after the first dose on day 1 than on day 6. This decrease in artemisinin plasma concentratio n is suggestive of an increase in metabolic capacity due to pronounced autoinduction.