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本文采用HPLC法同时测定血浆中美多心安(M)及α-羟美多心安(HM)浓度。狗iv及ig后M原形药物的药时变化分别呈二房室及一房室开放模型特征,拟合得各项药代动力学参数,绝对生物利用度为47.73士25.01%,活性代谢物HM的T1/2较M长,ig获得HM与M的AUC比率较iv者高(p<0.01),提示存在首过效应。人体口服M50mg每天两次至稳态时,M在肾功能正常与不全两组患者的T1/2、K值及血药浓度的差异无显著性。而HM在肾功能不全组较肾功能正常组患者其T1/2显著延长(p<0.05),各时间点血药浓度显著升高(p<0.01),HM在各患者的T1/2与其血清肌酐清除率的对数呈负相关关系。
In this paper, HPLC was used to determine the concentrations of Metoprolol (M) and α-Hydroxymethasone (HM) in plasma simultaneously. The pharmacokinetic parameters of two prototypes of iv and ig after M prototype were two-compartment and one-compartment open model respectively, and the pharmacokinetic parameters were fitted with the absolute bioavailability of 47.73 ± 25.01%. The active metabolites HM T1 / 2 was longer than M, and the AUC ratio of HM to M was higher than that of IV (p <0.01), suggesting the first pass effect. M50mg orally twice daily to the steady state, M in patients with normal renal function and incomplete T1 / 2, K value and plasma concentration was no significant difference. However, HM was significantly prolonged (P <0.05) in patients with renal insufficiency and renal dysfunction, and plasma concentrations of HM were significantly increased at each time point (p <0.01) Creatinine clearance was negatively correlated.