Study on the Pharmacokinetic-pharmacodynamic Model of Nisoldipine Controlled-release Patches in Spon-taneously Hypertensive Rats
10.6039/j.issn.1001-0408.2015.28.09
- VernacularTitle:尼索地平控释贴剂在自发性高血压大鼠体内的药动学-药效学结合模型的建立Δ
- Author:
Yang NIE
;
Liangkui XU
;
Bo LI
;
Junfang ZHU
;
Xinying CHEN
- Publication Type:Journal Article
- Keywords:
Nisoldipine;
Controlled-release patch;
Microdialysis;
Spontaneously hypertensive rat;
Pharmacokinetic-pharmaco-dynamic model
- From:
China Pharmacy
2015;(28):3915-3917
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To establish the pharmacokinetic-pharmacodynamic(PK-PD) model of Nisoldipine controlled-release patches(NCRP)in spontaneously hypertensive rats(SHR). METHODS:SHR were randomized into a patch(NCRP)group and a tablet(Nisoldipine tablets)group,with 6 rats in each group. The microdialysis probes were implanted in SHR. Each rat was given 5 mg nisoldipine. Plasma microdialysate was collected within 36 h after administration. HPLC was adopted to determine the plasma concentration of nisoldipine,and WinNonlin 5.3 was employed to calculate Pharmacokinetic parameters. With heart rate and blood pressure as pharmacodynamic indexes,PK-PD model study was conducted. RESULTS:Vs. nisoldipine tablets,NCRP has con-trolled release effect. The relationship between NCRP drug effect and effect-site concentration met the Sigmoid-Emax model. The main parameters of the PK-PD model for heart rate and systolic blood pressure were as follows as Emax of (2.65 ± 0.06) and (10.71 ± 0.87),EC50 of (83.65 ± 35.25) and (1.29 ± 0.26) ng/ml,γ of (0.83 ± 0.91) and (1.2 ± 0.35),Keo of (0.37 ± 0.53) and (0.91±0.24)h-1. CONCLUSIONS:PK-PD model of NCRP in SHR has been established successfully.
