三种剂量国产盐酸塞利洛尔片健康人体内药物动力学及参数相关性研究

Study on pharmacokinetics of domestic celiprolol hydrochloride in healthy volunteers

目的：测定盐酸塞利洛尔在人体内药代动力学特性及其３种不同剂量的药代动力学参数变化规律。方法：健康志愿者９名，３×３拉丁方设计，单剂量ｐｏ１００，２００，４００ｍｇ盐酸塞利洛尔片，采用反相高效液相色谱法测定不同时间的血药浓度，在计算机上以ＭＣＰＫＰ程序拟合，求算药代动力学参数。结果：１００，２００，４００ｍｇ国产盐酸塞利洛尔片的ｔ１／２Ｋ，Ｋ，ｔｍａｘ，ｃｍａｘ，ＡＵＣ０～∞分别为３．３７，３．４５和３．５６ｈ，０．２４，０．２１和０．２０ｈ－１，３．６４，３．３８和３．８７ｈ，１７７．５５，５０１．４和１１８８．５８ｎｇ·ｍｌ－１，１６１５．４１，４５０８．３８和１０８２８．５５μｇ·ｈ－１。结论：经方差分析，三剂量组的ｔ１／２ｋ，Ｋ，ｔｍａｘ等参数无显著差异（Ｐ＞０．０５），ｃｍａｘ，ＡＵＣ０～∞均不呈倍数变化。

OBJECTIVE: The pharmacokinetic characteristics of celiprolol hydrochloride and its change after different single dosing were investigated. METHOD: 100 mg,200 mg,and 400 mg celiprolol hydrochloride tablets were given orally in single dose to 9 healthy volunteers designed by 33 latin square.The plasma levels at given times were derermined by RPHPLC.The pharmacokinetic parameters were fitted and calculated by MCPKP program.HZRESULTS: t1/2k,K,tmax,cmax and AUC of 100,200 and 400 mg dometic celiprolol hydrochloride tablets were 3.37,3.45 and 3.56h;0.24,0.21 and 0.20 h-1;3.64,3.38 and 3.87 h;177.55,501.4 and 1188.58 ngml-1;1615.41,4508.38 and 10828.55 ghL-1,respectively.CONCLUSION: With analysis of variance,the parameters such as t1/2K,K and tmax in three kinds of dosage had no singnificant difference (P>0.05),cmax and AUC did not change multipl with the increase of dosage.