缬沙坦在不同肾功能高血压患者中的药动学和药效学

目的在不同肾功能的原发性高血压病人给予缬沙坦单次口服,研究缬沙坦的药代动力学与药效学.方法根据服药前血肌酐水平把原发性高血压病人分成肾功能正常与肾功能受损两组,单次予以缬沙坦160 mg口服,以服药后血药浓度及24 h动态血压监测结果研究缬沙坦的药动学与药效学.结果肾功能受损组的Cmax显著升高,而肾功能正常组的Tmax则较长,两组病人的T1/2无显著差异.两组病人服药后最大降压疗效则出现在服药后2～6 h.两组病人服药后降压效果均显著(P＜0.05).缬沙坦血药浓度与降压疗效呈正相关,而与服药前血肌酐水平无相关性.结论缬沙坦160 mg单次口服后在体内的清除过程不受肾功能影响,而吸收则受到影响.但降压疗效均显著.

Pharmacokinetics and pharmacodynamics of valsartan in hypertensive patients with normal and impaired renal functions

Objective To study the pharmacokinetics and pharmacodynamics of valsartan in hypertensives with impaired or non impaired renal functions. Methods According to serum creatinine levels, the enrolled subjects were divided into two groups. A single oral dose of 160 mg valsartan was administrated to each subject. Ambulatory blood pressure monitoring was carried out at the same time. Plasma concentration of valsartan was determined by HPLC. Results There was no marked difference between T1/2 in the subjects of the two groups after drug administration, while the Cmax of the renal dysfunction group was obviously higher than the other and Tmax shorter than that of the normal renal function group. The greatest antihypertensive effect appeared in 2 ~ 6 h after administration. The therapeutic effect was good in both groups. The hypotensive effect was positively related to the serum concentration of valsartan, and was not related to the serum creatinine concentration before administration. Conclusion The metabolism of valsartan in vivo was not affected in renal dysfunction, but the absorptive process was affected. Antihypertensive effect was obvious in both groups. Impaired renal function was not aggravated.