Objective To determine the in vivo pharmacokinetic parameters of PNS floating sustained-release tablets,and investigate the linear relationship between the in vivo release and the in vivo absorption in rabbits.Methods Ginsenoside Rgl was chosen as the index component,plasma concentrations of PNS were determined by HPLC method,to study the drug release in vivo and estimate pharmacokinetic parameters.Results Compared with common tablets,the tmax of PNS gastric floating sustained-release tablets was significantly prolonged,the Cmax was significantly decreased,MRT was delayed by about 3h,AUC was significantly increased.The regression equation about the in vivo release and the in vivo absorption was Y =1.2208 X + 6.3239(r=0.9023).Conclusion In vivo release of PNS gastric floating sustained-release tablets was stable,the sustained release effect is better,it can effectively improve the bioavailability of the preparation,and has a certain correlation in vivo and in vivo drug release process.

目的:建立高效液相色谱-质谱联用(HPLC-MS/MS)测定人血浆中卢非酰胺浓度的方法.方法:40名健康受试者随机分成4组,分别单剂量口服给药卢非酰胺片200,400,800,1200mg.血浆样品经乙腈沉淀蛋白提取分离,色谱柱为Ultimate(R)AQ-C18(100 mm×2.1mm,5μm,Welch Material Inc.);流动相为乙腈-5mmol·L-1乙酸胺水溶液(含0.1％甲酸)=32∶68;流速为0.30 mL·min-1;内标为埃索美拉唑.采用电喷雾离子源,以多反应监测(MRM)方式进行正离子检测.结果:卢非酰胺的血浆浓度在40～5 000ng·mL-1范围内线性良好,定量下限为40ng·mL-1,日内精密度(RSD)均≤8.20％,日间精密度(RSD)均≤6.35％,提取回收率为91.94％～96.48％.卢非酰胺呈非线性药动学特征,单剂量空腹口服给药卢非酰胺片200,400,800,1200mg后,Cmax分别为1803.50±528.06,2485.00±562.71,3710.00±965.50和4158.00±1181.91μg·L-1.AUC0-t分别为34522.13±9525.00,56138.53±18021.98,88848.53±23348.14和107058.03±34420.08 μg·h·L-1.结论:该法操作简单,灵敏,准确,重复性好,适用于卢非酰胺片临床药动学研究.从药动学研究可知,卢非酰胺在中国健康受试者中呈非线性药动学特征.

Objective To optimize the formulation of controlled-onset extended-release tablets of nicorandilby central composite design-response surface method. Methods The tablets containing nicorandil were prepared bydry-compression coating technique.The influence factors included the amount of HPMC, the amount of EC, and the ratio of lactose/MCC in coating film. The evaluation parameter was Q4 h and Q5 h . The possibly optimal formulation was predicted by response surface method. Results The OD was simulated using second-order polynomial equation and the r2was 0.970 1.Optimal prescription was as follows:HPMC 89.96 mg, EC 46.21 mg, Lactose/MCC 1.87.Bias between the observed and predicted values of the OD was within 0.43%. Conclusion The controlled-onset extended-release tablets of nicorandil can release drug quickly in vitro at the predetermined time.Central composite design-response surface method can be used to optimize the formulation and the model developed in this study was proved highly predictable.

目的 建立尼可地尔缓释片的含量测定方法.方法 采用HPLC法,Agilent TC-C18 (4.6mm×250mm,5μm)色谱柱,甲醇-水(48∶ 52)为流动相,流速1.0mL/min,检测波长254nm.结果 尼可地尔的线性范围为3.008μmL-18.048μ/mL,线性关系良好(r=0.9998);平均加样回收率为98.37％ (n =5),RSD =0.72％.结论 该方法简便、结果准确,适用于制剂中尼可地尔的含量测定与质量控制.

Objective To explore the absorption properties and kinetics of nicorandil from small intestinal segments. Methods The absorption kinetics and permeability of nicorandil under different conditions were investigated by HPLC via the in situ perfusing method in rats. Results There was no significant difference in Ka of nicorandil under different concentrations and different pH.The absorption rate in rats descended in order of jejunum,duodenum,ileum and colon, as (4.69±0.05)×10-2 ,(3.35 ±0.04) × 10-2 ,(2.66± 0.05) × 10-2 and (0.89± 0.08) × 10-2 .h-1 . Conclusion The absorption of nicorandil in intestine complies with the passive transport mechanism and first order kinetics.Nicorandil is well absorbed in the whole intestine and can be prepared as delayed release and controlled release forms.