Martin D E, Chapelsky M C, Ilson B, Tenero D, Boike S C, Zariffa N, Jorkasky D K
SmithKline Beecham Pharmaceuticals, Clinical Pharmacology Unit, Presbyterian Medical Center, University of Pennsylvania Health Care System, Philadelphia 19104, USA.
J Clin Pharmacol. 1998 Feb;38(2):129-37. doi: 10.1002/j.1552-4604.1998.tb04401.x.
This was an open-label, parallel group study to compare the pharmacokinetics of multiple oral doses of eprosartan in subjects with normal renal function (Clcr > 80 mL/min; n = 8) and patients with mild (Clcr 60-80 mL/min; n = 8), moderate (Clcr 30-59 mL/min; n = 15), or severe (Clcr < 30 mL/min; n = 3) renal insufficiency. Each subject received oral eprosartan 200 mg twice daily for 6 days and a single dose on day 7. Mean total maximum concentration (Cmax) and area under the concentration-time curve from 0 to 12 hours (AUC0-12) were similar for healthy subjects and those with mild renal impairment, but were an average of 25% to 35% and 51% to 55% greater for patients with moderate and severe renal impairment, respectively, compared with healthy subjects. Mean renal clearance (Clr), which was similar for healthy subjects and patients with mild renal impairment, was decreased an average of 41% and 95% in the groups with moderate and severe renal impairment, respectively, compared with normal subjects. Eprosartan was highly bound to plasma proteins in all groups; however, the unbound fraction was increased approximately two-fold in the group with severe renal impairment. Mean unbound Cmax and AUC0-12 were an average of 53% to 61% and 185% to 210% greater for the patients with moderate and severe renal impairment, respectively, compared with healthy subjects. Headache was the most common adverse experience reported in all subgroups. Eprosartan was safe and well tolerated regardless of degree of renal impairment. Cmax and AUC were increased and renal clearance decreased in patients with moderate to severe renal impairment in comparison to healthy subjects and patients with mild renal impairment. However, based on the moderate renal clearance and known safety profile of eprosartan, it is not necessary to adjust the dose of eprosartan in patients with renal insufficiency.
这是一项开放标签、平行组研究，旨在比较多次口服依普罗沙坦在肾功能正常（肌酐清除率>80 mL/分钟；n = 8）的受试者以及轻度（肌酐清除率60 - 80 mL/分钟；n = 8）、中度（肌酐清除率30 - 59 mL/分钟；n = 15）或重度（肌酐清除率<30 mL/分钟；n = 3）肾功能不全患者中的药代动力学。每位受试者每天口服依普罗沙坦200 mg，共6天，并在第7天服用单剂量。健康受试者和轻度肾功能损害患者的平均总最大浓度（Cmax）以及0至12小时浓度 - 时间曲线下面积（AUC0 - 12）相似，但与健康受试者相比，中度和重度肾功能损害患者的平均Cmax分别高出25%至35%，AUC0 - 12分别高出51%至55%。健康受试者和轻度肾功能损害患者的平均肾清除率（Clr）相似，但与正常受试者相比，中度和重度肾功能损害组的平均肾清除率分别降低了41%和95%。依普罗沙坦在所有组中均与血浆蛋白高度结合；然而，重度肾功能损害组的游离分数增加了约两倍。与健康受试者相比，中度和重度肾功能损害患者的平均游离Cmax分别高出53%至61%，AUC0 - 12分别高出185%至210%。头痛是所有亚组中报告的最常见不良事件。无论肾功能损害程度如何，依普罗沙坦都是安全且耐受性良好的。与健康受试者和轻度肾功能损害患者相比，中度至重度肾功能损害患者的Cmax和AUC增加，肾清除率降低。然而，基于依普罗沙坦适度的肾清除率和已知的安全性，肾功能不全患者无需调整依普罗沙坦的剂量。
