Lack of impact of artesunate on the disposition kinetics of sulfadoxine/pyrimethamine when the two drugs are concomitantly administered

Eur J Clin Pharmacol. 2007 May;63(5):457-62. doi: 10.1007/s00228-007-0278-4. Epub 2007 Feb 27.

Abstract

Objective: To determine the effect of artesunate (AT) on the disposition kinetics of sulfadoxine/pyrimethamine (SP) in humans.

Methods: In a randomized cross-over study, 16 healthy volunteers were given a dose of three SP tablets containing 500 mg of sulfadoxine (SDX) and 25 mg of pyrimethamine (PYR) (=SP group), while the second arm received three SP tablets + two AT tablets of 200 mg in total followed by 100 mg AT for the next 4 days (SP+AT group). Blood samples (100 microl) were collected by means of a finger prick and dried on filter paper. The blood spots were wrapped in polythene folders and stored at room temperature until analysis. The samples were assayed using high-performance liquid chromatographic methods.

Results: The peak concentration C(max)), time required to attain peak concentration (T(max)), half-life (t ((1/2))) and area under the plasma concentration-time curve (AUC) were determined. The C(max) of SDX were 92.9 and 98.9 microg/ml for the SP and SP+AT arms, respectively; for PYR, these were 0.86 and 0.79 microg/ml, respectively. The T(max) of SDX were 10 and 8 h for the SP and SP+AT arms, respectively; for PYR, these were 4.0 and 3.0 h, respectively. The AUC(0-288) of SDX were 15,840 and 18,876 microg/ml h for the SP and SP+AT arms, respectively; for PYR, they were 124 and 112 microg/ml h, respectively. The t ((1/2)) of values for SDX were 165 and 180 h for the SP and SP+AT arms, respectively; for PYR, these were 158 and 177 h, respectively. There was no statistically significant difference between the C(max), T(max), AUC(0-288) and t ((1/2)) between the two arms (p > 0.05).

Conclusion: Taking AT concomitantly with SP does not have any impact in the disposition of SP.

Publication types

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

MeSH terms

  • Adult
  • Antimalarials / pharmacokinetics*
  • Antimalarials / pharmacology*
  • Area Under Curve
  • Artemisinins / pharmacology*
  • Artesunate
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Drug Combinations
  • Drug Interactions
  • Half-Life
  • Humans
  • Malaria, Falciparum / drug therapy
  • Pyrimethamine / pharmacokinetics*
  • Sesquiterpenes / pharmacology*
  • Sulfadoxine / pharmacokinetics*

Substances

  • Antimalarials
  • Artemisinins
  • Drug Combinations
  • Sesquiterpenes
  • fanasil, pyrimethamine drug combination
  • Artesunate
  • Sulfadoxine
  • Pyrimethamine