Pharmacokinetics of artemether and dihydroartemisinin in healthy Pakistani male volunteers treated with artemether-lumefantrine

Malar J. 2010 Oct 11;9:275. doi: 10.1186/1475-2875-9-275.

Abstract

Background: Artemether-lumefantrine is one of the most widely used anti-malarial drug combinations in the world with excellent tolerability and cure rates in adult and paediatric patients with uncomplicated falciparum malaria. The aim of this study was to evaluate the pharmacokinetics of artemether and its active metabolite, dihydroartemisinin, in healthy Pakistani volunteers.

Methods: Twelve healthy male Pakistani subjects, aged 20 to 50, were recruited into the study. A fixed oral combination of artemether-lumefantrine (80-480 mg) was given as a single oral dose. Frequent blood samples were collected and artemether and dihydroartemisinin were quantified in human plasma using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. Drug concentration-time data were evaluated with non-compartmental analysis.

Results: Observed maximum concentrations (mean ± SD) of artemether and dihydroartemisinin were 184 ± 100 ng/mL and 126 ± 46 ng/mL, respectively. These concentrations were reached at 1.56 ± 0.68 hr and 1.69 ± 0.59 hr, respectively, after drug intake. The terminal elimination half-life of artemether and dihydroartemisinin were 2.00 ± 0.71 hr and 1.80 ± 0.31 hr, respectively. Apparent volume of distribution and oral clearance for artemether were estimated to 666 ± 220 L and 257 ± 140 L/hr. The same parameters were estimated to 702 ± 220 L and 269 ± 57 L/hr for dihydroartemisinin.

Conclusions: The overall pharmacokinetic properties of artemether and dihydroartemisinin in healthy Pakistani subjects are comparable to healthy subjects and patients from other populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antimalarials / administration & dosage*
  • Antimalarials / pharmacokinetics*
  • Artemether
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / administration & dosage*
  • Artemisinins / pharmacokinetics*
  • Chromatography, Liquid
  • Drug Combinations
  • Ethanolamines / administration & dosage*
  • Fluorenes / administration & dosage*
  • Human Experimentation
  • Humans
  • Male
  • Middle Aged
  • Pakistan
  • Plasma / chemistry
  • Tandem Mass Spectrometry
  • Time Factors

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • artenimol
  • Artemether