Combinations of artemisinin and quinine for uncomplicated falciparum malaria: Efficacy and pharmacodynamics

Combinations of artemisinin and quinine for uncomplicated falciparum malari a were studied. A total of 268 patients were randomized to 7 days of quinin e at 10 mg/kg of body weight three times a day (Q) or to artemisinin at 20 mg/kg of body weight followed by 3 (AQ3) or 5 (AQ5) days of quinine, Recrud escence rates were 16, 38, and 15% for the Q, AQ3, and AQ5 groups, respecti vely (P < 0.001). Recrudescence was associated with shorter parasite cleara nce time (PCT) and longer treatment after the blood smear bad become negati ve (eradication time). However, classification of patients to outcome-recru descence or radical cure-was correct in only 77% of patients. The populatio n kinetics of the parasitemia was estimated with nonlinear mixed-effect mod els. Several models were tested, but the best model was a monoexponential d ecline of the parasitemia in which the mean parasite elimination half-life was shorter after artemisinin (5.1 h; 95% confidence interval [CI], 4.9 to 5.2 h) than after quinine (8.0 h [95% CI, 7.5 to 8.3 h]). Attempts to simul ate the initial increase of the parasitemia did not result in better models ,vith a biologically plausible interpretation. Recrudescence was associated with slower parasite clearance and a higher simulated terminal parasitemia (P-term), The classification of patients to outcome groups based on P-term was correct in 78% of patients. The data suggest that parasite strains wit h reduced sensitivity to quinine are prevalent in Vietnam, with slower para site clearance and consequent recrudescence. A single dose of artemisinin i nduces rapid parasite reduction and lowers the value of P-term, but to prev ent recrudescence, this should be followed by quinine for at least 3 days a fter parasite clearance, or 5 days in total.