Yeun Ji-Sun, Kan Hye-Su, Lee Minyu, Kim Namsick, Oh Tae-Young, Nam Seung-Kwan, Choi Yoon Seok, Kwon In Sun, Hong Jang Hee
Clinical Trials Center, Chungnam National University Hospital, Daejeon 34134, Korea.
Center for Infectious Diseases Control, Korea Centers for Disease Control and Prevention, Cheongju 28159, Korea.
Transl Clin Pharmacol. 2020 Jun;28(2):102-108. doi: 10.12793/tcp.2020.28.e7. Epub 2020 Jun 15.
Bazedoxifene, used as bazedoxifene acetate, is a selective estrogen receptor modulator that selectively affects the uterus, breast tissue, bone metabolism, and lipid metabolism by antagonizing or enhancing estrogens in the estrogen receptor in the tissue. This study was conducted as an open, randomized, two-period, two-treatment, crossover design to compare the pharmacokinetic (PK) characteristics and tolerability of two bazedoxifene tablets when administered to 50 healthy Korean male volunteers. Enrolled subjects were randomly allocated to 2 sequences of a single oral administration of a test drug and a reference drug, or vice versa with a 14-day washout period between the two doses. Serial blood samples were collected over 96 h for PK analysis. Plasma concentration of bazedoxifene was assayed using liquid chromatography-tandem spectrometry mass. Forty-five participants completed the study with no clinically relevant safety issues. The peak concentrations (C, mean ± strandard deviation) of reference drug and test drug were 3.191 ± 1.080 and 3.231 ± 1.346 ng/mL, respectively, and the areas under the plasma concentration-time curve from 0 to the last measurable concentration (AUC) were 44.697 ± 21.168 ng∙h/mL and 45.902 ± 23.130 ng∙h/mL, respectively. The geometric mean ratios of test drug to reference drug and their 90% confidence intervals for C and AUC were 0.9913 (0.8828-1.1132) and 1.0106 (0.9345-1.0929), respectively. The incidence of adverse events between the two formulations was similar. The present study showed that PK and tolerability of two bazedoxifene tablet formulations were comparable when administered to healthy Korean male volunteers.
Clinical Research Information Service Identifier: KCT0003978.
巴多昔芬以醋酸巴多昔芬的形式使用，是一种选择性雌激素受体调节剂，通过拮抗或增强组织中雌激素受体的雌激素作用，选择性地影响子宫、乳腺组织、骨代谢和脂质代谢。本研究采用开放、随机、两期、双治疗、交叉设计，比较两种巴多昔芬片剂在50名健康韩国男性志愿者中给药时的药代动力学（PK）特征和耐受性。入选受试者被随机分配到单次口服试验药物和参比药物的2种顺序中，或反之，两剂之间有14天的洗脱期。在96小时内采集系列血样进行PK分析。采用液相色谱 - 串联质谱法测定巴多昔芬的血浆浓度。45名参与者完成了研究，无临床相关安全问题。参比药物和试验药物的峰浓度（C，均值±标准差）分别为3.191±1.080和3.231±1.346 ng/mL，从0至最后可测浓度的血浆浓度 - 时间曲线下面积（AUC）分别为44.697±21.168 ng∙h/mL和45.902±23.130 ng∙h/mL。试验药物与参比药物的C和AUC的几何平均比值及其90%置信区间分别为0.9913（0.8828 - 1.1132）和1.0106（0.9345 - 1.0929）。两种制剂之间不良事件的发生率相似。本研究表明，两种巴多昔芬片剂制剂在健康韩国男性志愿者中给药时的PK和耐受性具有可比性。
临床研究信息服务标识符：KCT0003978。
