BACKGROUND: @entity8185 ( @entity4601 ) is a component of @entity507 -based combination therapy (ACT), which is widely recommended for treatment of uncomplicated @entity9231 . @entity4601 is also the main metabolite of @entity15280 and @entity506 , both of which are used in ACT. Due to auto-induction metabolism, declining plasma concentrations after the repeated dosing have been reported for @entity507 (Qing-hao-su) and @entity15280 . This study was designed to evaluate the potential auto-induction metabolism of @entity4601 in healthy Chinese adults after multiple oral doses of @entity4601 . The polymorphic effects of @entity52084 ( @entity68568 ) and @entity22642 *2 ( @entity53292 ), the major enzymes involved in the metabolism of @entity4601 , on the pharmacokinetic profiles of @entity4601 and its metabolite was also studied. METHODS: Sixteen healthy Chinese subjects (four I399TT/802CC, four I399CC/802TT, four I399TT/802TT and four I399CT/802CT) received four recommended oral doses of Artekin, an ACT containing @entity4601 (80  mg/dose) and @entity26716 (PQ; 640  mg/dose), at 0, 6, 24 and 32  h. Plasma samples were analysed for @entity4601 and its metabolite using a validated liquid chromatography tandem mass spectrometric (LC-MS) method. RESULTS: @entity4601 and its glucuronidated metabolite @entity4601 - @entity367 were detected in @entity1 plasma after oral administration of @entity4601 -PQ. Compared with the first dose, the AUC0-t of the parent drug @entity4601 decreased significantly (P<0.01) with increased oral clearance (CL/F) after each repeated dose of DHA-PQ, whereas its metabolite @entity4601 - @entity367 did not change (P>0.05) in AUC0-t or Cmax. The phase II metabolic capability, calculated by the AUC0-t ratio of @entity4601 - @entity367 to the parent drug @entity4601 , increased 1.5-fold (90% CI, 1.3-1.7), 1.2-fold (90% CI, 1.1-1.3) and 1.7-fold (90% CI, 1.5-1.8) after the second, third and fourth dose, respectively. No polymorphic effect was found for @entity52084 ( @entity68568 ) and @entity22642 *2 ( @entity53292 ) on the pharmacokinetic profiles of @entity4601 and its metabolite @entity4601 - @entity367 . CONCLUSIONS: The auto-induction phase II metabolism of @entity4601 was present in healthy Chinese subjects after the recommended two-day oral doses of DHA-PQ (Artekin). The metabolic capability could recover after a 12-h dosing interval, which suggested that the alternative common three-day regimen (once daily) for DHA-PQ could probably lead to higher bioavailability of @entity4601 . The polymorphism of @entity52084 ( @entity68568 ) and @entity22642 *2 ( @entity53292 ) may not be a concern during the treatment with @entity4601 .

The effect of UGTs polymorphism on the auto-induction phase II metabolism-mediated pharmacokinetics of @entity8185 in healthy Chinese subjects after oral administration of a fixed combination of XXXX - @entity26716 .

@entity68568 :: ('|SUB|I,C|399|T', 'ProteinMutation') :: ['I399C>T'] @entity1 :: ('9606', 'Species') :: ['human'] @entity52084 :: ('54600', 'Gene') :: ['UGT1A9'] @entity26716 :: ('MESH:C034759', 'Chemical') :: ['piperaquine'] @entity8185 :: ('MESH:C039060', 'Chemical') :: ['Dihydroartemisinin'] @entity4601 :: ('CHEBI:16016', 'Chemical') :: ['DHA'] @entity9231 :: ('MESH:D016778', 'Disease') :: ['falciparum malaria'] @entity507 :: ('MESH:C031327', 'Chemical') :: ['artemisinin'] @entity53292 :: ('c|SUB|C|802|T', 'DNAMutation') :: ['802C>T'] @entity506 :: ('MESH:C039726', 'Chemical') :: ['artesunate'] @entity15280 :: ('MESH:C032942', 'Chemical') :: ['artemether'] @entity22642 :: ('7364', 'Gene') :: ['UGT2B7'] @entity367 :: ('CHEBI:18237', 'Chemical') :: ['Glu']
@entity8185 :: (MESH:C039060,Chemical) :: ['dihydroartemisinin']
