Bramson Candace, Ouellet Daniele, Roman Doina, Randinitis Edward, Gardner Mark J
Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
J Clin Pharmacol. 2006 Jan;46(1):29-36. doi: 10.1177/0091270005283278.
Lasofoxifene, a selective estrogen receptor modulator for osteoporosis management, is metabolized primarily by hepatic oxidation and conjugation. This study compared the pharmacokinetics of 0.25 mg lasofoxifene in subjects with mild (Child-Pugh grade A, n = 6) or moderate (Child-Pugh grade B, n = 6) hepatic impairment and healthy volunteers (n = 6). Analysis of variance was used to calculate 90% confidence intervals for the ratios (impaired/healthy) of least squares mean log maximum plasma concentration (C(max)) and area under the curve (AUC) values. Lasofoxifene pharmacokinetics was similar between healthy and mild hepatic impairment subjects: ratios of C(max) and AUC from 0 to infinity (AUC([0-infinity])) were 101% (75.0-138) and 95.5% (77.9-117), respectively. In subjects with moderate hepatic impairment, ratios of C(max) and AUC([0-infinity]) were 121% (89.6-165) and 138% (112-169), respectively; mean terminal half-life was 252 hr compared to 193 hr in healthy subjects. Dose adjustment should not be required for subjects with mild to moderate hepatic impairment.
拉索昔芬是一种用于治疗骨质疏松症的选择性雌激素受体调节剂，主要通过肝脏氧化和结合进行代谢。本研究比较了0.25毫克拉索昔芬在轻度（Child-Pugh A级，n = 6）或中度（Child-Pugh B级，n = 6）肝功能损害患者及健康志愿者（n = 6）中的药代动力学。采用方差分析计算最小二乘均值对数最大血浆浓度（C(max)）和曲线下面积（AUC）值的比值（肝功能损害组/健康组）的90%置信区间。健康受试者与轻度肝功能损害受试者的拉索昔芬药代动力学相似：C(max)和0至无穷大的AUC（AUC([0-无穷大])）的比值分别为101%（75.0 - 138）和95.5%（77.9 - 117）。在中度肝功能损害患者中，C(max)和AUC([0-无穷大])的比值分别为121%（89.6 - 165）和138%（112 - 169）；平均终末半衰期为252小时，而健康受试者为193小时。轻度至中度肝功能损害患者可能无需调整剂量。
