title: Preliminary investigation of the contribution of CYP2A6, CYP2B6, and UGT1A9 polymorphisms on artesunate-mefloquine treatment response in Burmese patients with Plasmodium falciparum malaria.
abstract: CYP2A6, CYP2B6, and UGT1A9 genetic polymorphisms and treatment response after a three-day course of artesunate-mefloquine was investigated in 71 Burmese patients with uncomplicated Plasmodium falciparum malaria. Results provide evidence for the possible link between CYP2A6 and CYP2B6 polymorphisms and plasma concentrations of artesunate/dihydroartemisinin and treatment response. In one patient who had the CYP2A6*1A/*4C genotype (decreased enzyme activity), plasma concentration of artesunate at one hour appeared to be higher, and the concentration of dihydroartemisinin was lower than for those carrying other genotypes (415 versus 320 ng/mL). The proportion of patients with adequate clinical and parasitologic response who had the CYP2B6*9/*9 genotype (mutant genotype) was significantly lower compared with those with late parasitologic failure (14.0% versus 19.0%). Confirmation through a larger study in various malaria-endemic areas is required before a definite conclusion on the role of genetic polymorphisms of these drug-metabolizing enzymes on treatment response after artesunate-based combination therapy can be made.
authors.affiliation: Chulabhorn International College of Medicine, and Thailand Center of Excellence on Drug Discovery and Development Thammasat University (Rangsit Campus), Patumthani, Thailand; Mae Sot General Hospital, Mae Sot District, Tak Province, Thailand.
authors.forename: Papichaya
authors.initials: P
authors.lastname: Phompradit
authors.affiliation: Chulabhorn International College of Medicine, and Thailand Center of Excellence on Drug Discovery and Development Thammasat University (Rangsit Campus), Patumthani, Thailand; Mae Sot General Hospital, Mae Sot District, Tak Province, Thailand.
authors.forename: Poonuch
authors.initials: P
authors.lastname: Muhamad
authors.affiliation: Chulabhorn International College of Medicine, and Thailand Center of Excellence on Drug Discovery and Development Thammasat University (Rangsit Campus), Patumthani, Thailand; Mae Sot General Hospital, Mae Sot District, Tak Province, Thailand.
authors.forename: Anurak
authors.initials: A
authors.lastname: Cheoymang
authors.affiliation: Chulabhorn International College of Medicine, and Thailand Center of Excellence on Drug Discovery and Development Thammasat University (Rangsit Campus), Patumthani, Thailand; Mae Sot General Hospital, Mae Sot District, Tak Province, Thailand kesaratmu@yahoo.com.
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; D004359:Drug Therapy, Combination; D005260:Female; D015870:Gene Expression; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000469:parasitology; D008297:Male; D015767:Mefloquine / Q000627:therapeutic use*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D000090264:UDP-Glucuronosyltransferase 1A9
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C000715591:UGT1A9 protein, human; D000077332:Artesunate; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; C585599:CYP2B6 protein, human; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D015767:Mefloquine