title: Orally formulated artemisinin in healthy fasting Vietnamese male subjects: a randomized, four-sequence, open-label, pharmacokinetic crossover study.
abstract: BACKGROUND
  Artemisinin derivatives are used in antimalarial drug combination therapy. Artemisinin and piperaquine have recently been proven to be prospective candidates for combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria.
  
  
  OBJECTIVE
  The goal of this study was to evaluate the relative bioavailability and to characterize the pharmacokinetic properties of a new micronized powder formulation of artemisinin against the previous standard Vietnamese formulation when administered as a single oral dose or in combination with piperaquine.
  
  
  METHODS
  This was a single-center, randomized, 4-sequence, open-label, crossover study conducted in 15 healthy male Vietnamese volunteers under fasting conditions with a washout period of 3 weeks between study visits. A single oral dose of 160 or 500 mg of artemisinin was administered alone or in combination with piperaquine. Potential adverse events were monitored daily by the clinician and by using laboratory test results. Frequent blood samples were drawn for 12 hours after dose. Artemisinin was quantified in plasma using LC-MS/MS. Pharmacokinetic parameters were computed from the plasma concentration-time profiles using a noncompartmental analysis method.
  
  
  RESULTS
  Pharmacokinetic parameters T(max), C(max), AUC(0-∞), V(d)/F, CL/F, and t(1/2) (mean [SD]) for the new formulation of artemisinin were 1.83 (0.88) hours, 178 (97) ng/mL, 504 (210) h × ng/mL, 1270 (780) L, 401 (260) L/h, and 2.21 (0.29) hours, respectively. The mean percentage of the test/reference formulation ratio for the logarithmically transformed values of C(max), AUC(0-last,) and AUC(0-∞) were 121% (90% CI, 92.5-158), 122% (90% CI, 101-148), and 120% (90% CI, 98.0-146), respectively.
  
  
  CONCLUSIONS
  This single-dose study found that the dose-normalized C(max), AUC(0-last), and AUC(0-∞) mean geometric differences between the test and reference formulations were relatively small (<40%) and will probably not have a clinical impact in the treatment of malaria infections.
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.forename: Warunee
authors.initials: W
authors.lastname: Hanpithakpong
authors.forename: Nguyen Thanh
authors.initials: NT
authors.lastname: Truong
authors.forename: Nguyen Thi
authors.initials: NT
authors.lastname: Dung
authors.forename: Pham Van
authors.initials: PV
authors.lastname: Toi
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Niklas
authors.initials: N
authors.lastname: Lindegardh
authors.forename: Joel
authors.initials: J
authors.lastname: Tarning
authors.forename: Michael
authors.initials: M
authors.lastname: Ashton
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D037621:Artemisinins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014744:Vietnam; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin