摘要
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。
A HPLC method have been used for the simultaneous determination of metoprolol(M)and α-hydroxymetoprolol (HM) in plasma. After single iv and ig administration of M to dogs in different time, concentration-time curves of M could be fixed as two and one compartment open model, respectively. The pharmacokinetic parameters of M have been obtained.The systemic oral bioavailability of M was 47 .73 ±25.01% .The T1/2 of HM,the main active metabolite, was longer than the parent drug. The mean ratio, AUC (HM) /AUC (M), was higher in ig doses than iv doseS(p<0.01),indicating the presystemic metabolism of M in ig doses. Human pharmacokinetic study in patients with normal renal function (group A ) and impaired renal function (group B) after oral administration of M 50 mg twice daily in steady-state showed that no statistical difference was found in T1/2,K and concentrations in different time of M between two groups.But in thegroup B, T1/2 of HM was longer (p<0.05), concentration in different time of HM was high (p<0.01) than group A, There was a linear relationShip between T1/2 of HM and logarithm of CCr (r= -0.832, p=0.0008).
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
1990年第3期165-170,共6页
The Chinese Journal of Clinical Pharmacology
关键词
美多心安
肾功能
药代动力学
metoprolol
α-hydroxymetoprolol
HPLC
pharmacokinetic
renal function
