Ji Misuk, Kim Kwang-Rae, Lee Woochang, Choe Wonho, Chun Sail, Min Won-Ki
Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea.
Department of Obstetrics and Gynecology, Mizmedi Hospital, Seoul, Korea.
J Korean Med Sci. 2016 Feb;31(2):310-4. doi: 10.3346/jkms.2016.31.2.310. Epub 2016 Jan 26.
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.
细胞色素P450 2D6（CYP2D6）主要负责枸橼酸氯米芬（CC）的代谢。本研究的目的是调查CYP2D6基因分型、CC及其主要代谢产物浓度与不孕症患者药物反应之间的关系。我们研究了42例仅接受CC治疗的排卵功能障碍患者。患者在月经周期的第3至7天接受100mg/天的CC剂量。进行了CYP2D6基因分型以及CC和主要代谢产物浓度的测定。根据一个周期的排卵反应，将患者分为CC反应者或无反应者。32例患者为CC反应者，10例患者经过1个周期治疗后为无反应者。同一组内CC浓度高度可变，但与反应者相比，无反应者的（E）-氯米芬浓度显著降低，活性代谢产物浓度有下降趋势。9例中间代谢型患者均为反应者。我们证实，CC和代谢产物浓度根据排卵状态而有所不同。然而，我们的结果并未提供证据表明CYP2D6基因多态性对药物反应或CC浓度有影响。
