硝苯啶普通型和缓释型的药代动力学和药效学研究

THE PHARMAC0KINETIC AND PHARMC0DYNAMIC STUDIES OF NORMAL RELEASE AND SLOW RELEASE FORMULATIONS OF NIFEDIPINE

本文报道硝苯啶普通和缓释两种剂型在原发性高血压患者的药代动力学和药效学变化。12例患者随机分为2组,分别单次口服硝苯啶普通片或缓释片20mg。硝苯啶血浓度由高效液相色谱-紫外检测器检测,并观察卧位血压心率变化。结果:普通片达峰时间(tmax)1.59±0.16h较缓释片4.07±0.62h早,p<0.01;普通片峰浓度(Cmax) 57.9±4.78ng/ml较缓释片30.19±6.83ng/ml高,p<0.001普通片消除半衰期(t1/2ke)1.82±0.44h较缓释片3.70±1.15h短,p<0.001。两种剂型最大降压幅度无显著性差异,P>0.05,但后者降压作用的维持时间延长。两种剂型血药浓度与收缩压(SBP)、舒张压(DBP)和心率(HR)变化呈正相关。缓释片的副反应(如心率增快)小于普通片。总之,缓释片具有降压作用长,血药浓度平稳,副反应小,且能减少服药次数的优点。

pharmcokinetic and pharmcodynamic effects of two formu-lations of nifedipine were studied in 12 hospitalized male patients withmild to moderate essential hypertension, mean age 49 years the patientswere randomized in that 6 patients received 20mg nifedipine slow release formwhile the other 6 received 20mg nifedipine normal release form. The drugswere given single dose. The nifedipine plasma concentrations were deter-mined by high pressure liquid chromatography with an ultraviolet detector. Changes of supine blood pressure( BP) and heart rate (HR) were re-corded by an automatic blood pressure monitor. The results showed: 1.The maxium plasma concentrations( Cmax) were higher and were attainedmore rapidly in the patients who received the normal release tablet thanin those to whom the slow release tablet was given( p<0.001) . 2. Theeliminatinn half life(t1/2 ke)of normal release tablet was shorter than thatof the slow release tablet( p<0.01) 3. The maxium fall in BP level obser-ved with the slow release tablet did not differ from that with the normalrelease tablet,but BP lowering effect lasted much longer with the slowrelease form .The plasma nifedipine concentrations were strongly correla-ted with the decrease in BP and the increase in HR. On the basis of theabove pharmacokinetic difference, a prolonged lowering effect on BP wouldbe expected with the twice daily dosage of the slow release tablet of nife-dipine and side effects such as palpitations caused by high Cmax could beavoided.