J Korean Med Sci.  2016 Feb;31(2):310-314. 10.3346/jkms.2016.31.2.310.

Genetic Polymorphism of CYP2D6 and Clomiphene Concentrations in Infertile Patients with Ovulatory Dysfunction Treated with Clomiphene Citrate

• Ji M
• Kim KR
• Lee W
• Choe W
• Chun S
• Min WK

• KMID: 2360058
• DOI: http://doi.org/10.3346/jkms.2016.31.2.310

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.

Keyword

Clomiphene; Ovulation Induction; Cytochrome P-450 CYP2D6

MeSH Terms

Adult
Chromatography, High Pressure Liquid
Clomiphene/blood/metabolism/*therapeutic use
Cytochrome P-450 CYP2D6/*genetics
Estrogen Antagonists/analysis/metabolism/therapeutic use
Female
Genotype
Humans
Infertility/*drug therapy/genetics
Ovulation Induction
Phenotype
*Polymorphism, Genetic
Republic of Korea
Tandem Mass Spectrometry
Clomiphene
Cytochrome P-450 CYP2D6
Estrogen Antagonists

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