进口尼索地平在中国人的人体药代动力学研究

PHARMACOKINETICS OF NISOLDIPINE IMPORTED IN CHINESE HEALTHY VOLUNTEERS

本研究改良了测定血浆中尼索地平浓度的反相ＨＰＬＣ方法，进行了７例健康志愿者单剂量口服尼索地平片４０ｍｇ，其中两名志愿者又服尼索地平片５ｍｇ，早晚各一次，连续４ｄ后，第５ｄ服４０ｍｇ的临床药代动力学研究。志愿者在服药前（多剂量组第５ｄ服药前）及服药后０．５，１，１．５，２，３，４，６，８，１２，２４ｈ取血，进行ＨＰＬＣ分析，结果表明：单剂量组和多剂量组药物吸收良好，单剂量组Ｔｍａｘ为１．８７±０．５３ｈ，Ｃｍａｘ为２３．６２±２．６４μｇ／Ｌ，ＡＵＣ＿（０－∞）为１３３．８±５０．９０μｇ·ｈ－１·Ｌ－１，Ｔ１／２ｔｅｒｍｉｎａｌ为９．９９±３．００ｈ；两例多剂量组的Ｔｍａｘ分别为１．４０和１．８９ｈ，Ｃｍａｘ为２０．６４和２１．１５μｇ／Ｌ，ＡＵＣ＿（０－∞）为１１２．７和１１０．３μｇ·ｈ－１·Ｌ－１，Ｔ１／２ｔｅｒｍｉｎａ１，为６．５０和１１．９９ｈ。

Pharmacokinetic characteristics of nisoldipine(Bayer,Germany)were studied in 7 Chinese healthy volunteers.They were given orally a single-dose(40 mg)of nisoldipine,two of them took a short-term multiple-dose(5 mg twice daily for four days followed by 40 mg nisoldipine on the fifth day).Blood samples were drawn beforedrug administration and 0.5,1,1.5,2,3,4,6,8,12,24 h after 40 mg dose.A selective RP-HPLC method with a UV spectrophotometric detector was established to determine plasma nisoldipine concentration Tmax for single-dose group was 1.87±0.53 h Cmax was 23.62±2.64μg/1,AUC0-∞ was 133.8±50.9μg·h-1·L T1/2 term was9.99±3.00h.For the two volunteers in multiple-dose group,Tmax was 1.40,1.89 h respectively,Cmax was20.64,21.15μg/L,AUC0-∞ 112.7,110.3μg·h-1·L-1 T1/2 term was 6.5,11.99 h respectively.