Tenero D M, Martin D E, Miller A K, Ilson B, Boike S C, Zariffa N, Jorkasky D K
Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA.
Br J Clin Pharmacol. 1998 Sep;46(3):267-70. doi: 10.1046/j.1365-2125.1998.00778.x.
To compare the pharmacokinetics of eprosartan between young (18-45 years) and elderly (65 years) men and between young men and young, premenopausal women (18-45 years).
Twenty-four subjects (eight subjects/group) received a single 200 mg eprosartan oral dose followed by serial blood sampling over 24 h.
Eprosartan was safe and well tolerated. There were no apparent differences in the pharmacokinetics of eprosartan between young females and young males or in the plasma protein binding of eprosartan (98%) for the three groups. On average, AUC (0,infinity) and Cmax values were approximately 2-fold higher in elderly men than young men [AUC (0,infinity) 95% CI: 1.22, 4.34; Cmax 95% CI: 0.98, 4.001. Similarly, unbound AUC (0,infinity) and Cmax values were, on average, approximately 2-fold higher in elderly men than young men [unbound AUC (0,infinity) 95% CI: 1.29, 4.44; unbound Cmax 95% CI: 1.02, 4.12]. tmax was delayed in the elderly men compared with young men, with a median difference of 2.5 h (95% CI: 1.00, 3.01 h).
No gender differences were observed in the pharmacokinetics of eprosartan. There were approximately two fold higher AUC and Cmax values for eprosartan observed in elderly men as compared with young men, most likely due to increased bioavailability of eprosartan in the elderly. Based on the excellent safety profile in the elderly in Phase III clinical trials (doses up to 1200 mg eprosartan) eprosartan can be safely administered to elderly hypertensive patients without an initial dose adjustment. Subsequently, the dose of eprosartan, as for other antihypertensive agents, may be individualized based on tolerability/response.
比较年轻男性（18 - 45岁）与老年男性（65岁及以上）以及年轻男性与年轻绝经前女性（18 - 45岁）之间依普罗沙坦的药代动力学。
24名受试者（每组8名）口服单剂量200毫克依普罗沙坦，随后在24小时内进行系列血样采集。
依普罗沙坦安全且耐受性良好。年轻女性和年轻男性之间依普罗沙坦的药代动力学以及三组的依普罗沙坦血浆蛋白结合率（98%）均无明显差异。平均而言，老年男性的AUC(0,∞)和Cmax值比年轻男性高约2倍[AUC(0,∞) 95% CI：1.22, 4.34；Cmax 95% CI：0.98, 4.00]。同样，老年男性的非结合AUC(0,∞)和Cmax值平均比年轻男性高约2倍[非结合AUC(0,∞) 95% CI：1.29, 4.44；非结合Cmax 95% CI：1.02, 4.12]。与年轻男性相比，老年男性的tmax延迟，中位数差异为2.5小时（95% CI：1.00, 3.01小时）。
未观察到依普罗沙坦药代动力学存在性别差异。与年轻男性相比，老年男性中依普罗沙坦的AUC和Cmax值大约高两倍，最可能是由于依普罗沙坦在老年人中的生物利用度增加。基于III期临床试验中老年人的良好安全性（依普罗沙坦剂量高达1200毫克），依普罗沙坦无需初始剂量调整即可安全用于老年高血压患者。随后，与其他抗高血压药物一样，依普罗沙坦的剂量可根据耐受性/反应进行个体化调整。
