Tenero D, Martin D, Chapelsky M, Ilson B, Boike S, Patterson S, Keogh J, Rodriguez S, Jorkasky D
Department of Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Pharmacotherapy. 1998 Jan-Feb;18(1):42-50.
To evaluate the pharmacokinetics and plasma protein binding of eprosartan in hepatic disease.
Single-dose, parallel-group study.
Oklahoma Foundation for Digestive Research, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Eight healthy subjects with normal hepatic function and eight patients with hepatic disease.
All subjects received a single oral dose of eprosartan 100 mg.
Eprosartan plasma concentrations were quantified by high-performance liquid chromatography; plasma protein binding was determined by ultrafiltration. Using analysis of variance, point estimates (PE) and 90% CIs were calculated. Total and unbound maximum concentrations and degree of plasma protein binding were similar for both groups. Total area under the plasma concentration-time curve (AUC0-t) was approximately 40% higher for the group with hepatic disease (PE 1.42, 90% CI 0.94-2.14). Similarly, unbound AUC0-t was approximately 50% higher (PE 1.53, 90% CI 0.98-2.39).
Eprosartan was safe and well tolerated by both groups. Based on the increase in AUC in patients with hepatic disease compared with those with normal hepatic function, the dosage of eprosartan in patients with hepatic disease should be individualized based on tolerability and response.
评估依普罗沙坦在肝脏疾病中的药代动力学及血浆蛋白结合情况。
单剂量、平行组研究。
俄克拉荷马大学健康科学中心俄克拉荷马消化研究基金会，俄克拉荷马城，俄克拉荷马州。
8名肝功能正常的健康受试者和8名肝脏疾病患者。
所有受试者均口服单剂量100毫克依普罗沙坦。
采用高效液相色谱法定量测定依普罗沙坦血浆浓度；通过超滤法测定血浆蛋白结合率。使用方差分析计算点估计值（PE）和90%置信区间（CI）。两组的总浓度和非结合态最大浓度以及血浆蛋白结合程度相似。肝脏疾病组的血浆浓度-时间曲线下总面积（AUC0-t）比健康组高约40%（PE 1.42，90% CI 0.94 - 2.14）。同样，非结合态AUC0-t高约50%（PE 1.53，90% CI 0.98 - 2.39）。
两组对依普罗沙坦均耐受良好且安全。与肝功能正常者相比，肝脏疾病患者的AUC有所增加，因此肝脏疾病患者的依普罗沙坦剂量应根据耐受性和反应情况个体化调整。
