Multiple dose pharmacokinetics of artemether in Chinese patients with uncomplicated falciparum malaria

Int J Antimicrob Agents. 1999 Jul;12(2):151-8. doi: 10.1016/s0924-8579(99)00063-1.

Abstract

Multiple dose pharmacokinetics of artemether and dihydroartemisinin were investigated in chinese patients treated for malaria. They received over 2 days either 4 x 80 mg artemether orally (n = 48) or 4 x 80-480 mg co-artemether (n = 40), a combination of artemether and lumefantrine (benflumetol). Lag time = 0.48 h (mean), Cmax after first dose = 157 ng/ml, t(max) = 1.73 h and elimination half-life = 1.16 h. The lag and absorption times were 0.5 h longer for co-artemether compared with artemether. Dihydroartemisinin paralleled artemether pharmacokinetics. Artemether Cmax after the last dose was one-third of the Cmax after the first dose while, inversely, dihydroartemisinin Cmax increased over time. We suggest that auto-induction of gut mucosa enzymes and/or liver enzymes causes a time-dependent increase in first-pass metabolisation of artemether.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials / pharmacokinetics*
  • Antimalarials / therapeutic use
  • Artemether
  • Artemisinins*
  • China
  • Double-Blind Method
  • Drug Evaluation
  • Drug Therapy, Combination
  • Ethanolamines / pharmacokinetics
  • Ethanolamines / therapeutic use
  • Female
  • Fluorenes / pharmacokinetics
  • Fluorenes / therapeutic use
  • Humans
  • Lumefantrine
  • Malaria, Falciparum / blood*
  • Malaria, Falciparum / drug therapy
  • Male
  • Middle Aged
  • Models, Chemical
  • Sesquiterpenes / pharmacokinetics*
  • Sesquiterpenes / therapeutic use
  • Time Factors

Substances

  • Antimalarials
  • Artemisinins
  • Ethanolamines
  • Fluorenes
  • Sesquiterpenes
  • artenimol
  • Artemether
  • Lumefantrine