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

Antimicrob Agents Chemother. 2000 May;44(5):1302-8. doi: 10.1128/AAC.44.5.1302-1308.2000.


Combinations of artemisinin and quinine for uncomplicated falciparum malaria were studied. A total of 268 patients were randomized to 7 days of quinine 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. Recrudescence rates were 16, 38, and 15% for the Q, AQ3, and AQ5 groups, respectively (P < 0.001). Recrudescence was associated with shorter parasite clearance time (PCT) and longer treatment after the blood smear had become negative (eradication time). However, classification of patients to outcome-recrudescence or radical cure-was correct in only 77% of patients. The population kinetics of the parasitemia was estimated with nonlinear mixed-effect models. Several models were tested, but the best model was a monoexponential decline 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 simulate the initial increase of the parasitemia did not result in better models with 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 with reduced sensitivity to quinine are prevalent in Vietnam, with slower parasite clearance and consequent recrudescence. A single dose of artemisinin induces rapid parasite reduction and lowers the value of P(term), but to prevent recrudescence, this should be followed by quinine for at least 3 days after parasite clearance, or 5 days in total.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials / pharmacokinetics
  • Antimalarials / therapeutic use*
  • Artemisinins*
  • Child
  • Drug Therapy, Combination
  • Female
  • Humans
  • Malaria, Falciparum / drug therapy*
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Quinine / pharmacokinetics
  • Quinine / therapeutic use*
  • Sesquiterpenes / pharmacokinetics
  • Sesquiterpenes / therapeutic use*
  • Treatment Outcome


  • Antimalarials
  • Artemisinins
  • Sesquiterpenes
  • artemisinin
  • Quinine