title: Lack of impact of artesunate on the disposition kinetics of sulfadoxine/pyrimethamine when the two drugs are concomitantly administered.
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).
  
  
  CONCLUSIONS
  Taking AT concomitantly with SP does not have any impact in the disposition of SP.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University College of Health Sciences, P.O. Box 65013, Dar es Salaam, Tanzania. ominzi@muchs.ac.tz
authors.forename: O M S
authors.initials: OM
authors.lastname: Minzi
authors.forename: A
authors.initials: A
authors.lastname: Gupta
authors.forename: A F
authors.initials: AF
authors.lastname: Haule
authors.forename: G A B
authors.initials: GA
authors.lastname: Kagashe
authors.forename: A Y
authors.initials: AY
authors.lastname: Massele
authors.forename: L L
authors.initials: LL
authors.lastname: Gustafsson
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D011739:Pyrimethamine / Q000493:pharmacokinetics*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013413:Sulfadoxine / Q000493:pharmacokinetics*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine