title: Genetic Polymorphism of CYP2D6 and Clomiphene Concentrations in Infertile Patients with Ovulatory Dysfunction Treated with Clomiphene Citrate.
abstract: CYP2D6 is primarily responsible for the metabolism of clomiphene citrate (CC). The purpose of the present study was to investigate the relationship between CYP2D6 genotypes, concentrations of CC and its major metabolites and drug response in infertility patients. We studied 42 patients with ovulatory dysfunction treated with only CC. Patients received a dose of 100 mg/day CC on days 3-7 of the menstrual cycle. CYP2D6 genotyping and measurement of CC and the major metabolite concentrations were performed. Patients were categorized into CC responders or non-responders according to one cycle response for the ovulation. Thirty-two patients were CC responders and 10 patients were non-responders with 1 cycle treatment. The CC concentrations were highly variable within the same group, but non-responders revealed significantly lower (E)-clomiphene concentration and a trend of decreased concentrations of active metabolites compared to the responders. Nine patients with intermediate metabolizer phenotype were all responders. We confirmed that the CC and the metabolite concentrations were different according to the ovulation status. However, our results do not provide evidence for the contribution of CYP2D6 polymorphism to either drug response or CC concentrations.
authors.affiliation: Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Misuk
authors.identifier: 0000-0001-5292-5185
authors.initials: M
authors.lastname: Ji
authors.affiliation: Department of Obstetrics and Gynecology, Mizmedi Hospital, Seoul, Korea.
authors.forename: Kwang-Rae
authors.identifier: 0000-0002-2531-2217
authors.initials: KR
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Woochang
authors.identifier: 0000-0003-3956-6397
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Wonho
authors.identifier: 0000-0002-9685-4291
authors.initials: W
authors.lastname: Choe
authors.affiliation: Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sail
authors.identifier: 0000-0002-5792-973X
authors.initials: S
authors.lastname: Chun
authors.affiliation: Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Won-Ki
authors.identifier: 0000-0002-5158-2130
authors.initials: WK
authors.lastname: Min
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D002996:Clomiphene / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004965:Estrogen Antagonists / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D007246:Infertility / Q000188:drug therapy* / Q000235:genetics; D010062:Ovulation Induction; D010641:Phenotype; D011110:Polymorphism, Genetic; D056910:Republic of Korea; D053719:Tandem Mass Spectrometry
chemical_list: D004965:Estrogen Antagonists; D002996:Clomiphene; D019389:Cytochrome P-450 CYP2D6
keywords: Clomiphene; Cytochrome P-450 CYP2D6; Ovulation Induction
references.citation: Hum Reprod. 2005 Aug;20(8):2043-51
references.pmid: 15878925
references.citation: Anal Bioanal Chem. 2011 Jul;400(10):3429-41
references.pmid: 21533795
references.citation: Cancer Genet Cytogenet. 2010 Jul 1;200(1):34-9
references.pmid: 20513532
references.citation: Hum Reprod Update. 1996 Nov-Dec;2(6):483-506
references.pmid: 9111183
references.citation: Ther Drug Monit. 2006 Jun;28(3):382-7
references.pmid: 16778723
references.citation: Clin Chem. 2000 Aug;46(8 Pt 1):1072-7
references.pmid: 10926885
references.citation: Hum Fertil (Camb). 2001;4(3):145-51
references.pmid: 11591271
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2004 Jan;369(1):23-37
references.pmid: 14618296
references.citation: Int J Gynaecol Obstet. 2010 Oct;111(1):95-100
references.pmid: 20848729
references.citation: J Clin Endocrinol Metab. 2013 Oct;98(10):4170-5
references.pmid: 23979947
references.citation: Clin Exp Reprod Med. 2013 Jun;40(2):95-9
references.pmid: 23875166
references.citation: Nat Rev Genet. 2004 Sep;5(9):669-76
references.pmid: 15372089
references.citation: J Clin Pharmacol. 2009 Feb;49(2):147-54
references.pmid: 19033451
references.citation: Hum Mol Genet. 2012 Mar 1;21(5):1145-54
references.pmid: 22108178
references.citation: Drug Metab Dispos. 2009 Jul;37(7):1464-70
references.pmid: 19364831
references.citation: Drug Metab Pharmacokinet. 2008;23(2):101-5
references.pmid: 18445989
references.citation: Eur J Obstet Gynecol Reprod Biol. 2006 Jun 1;126(2):201-5
references.pmid: 16337728