中国健康志愿者口服福辛普利的药代动力学研究

目的　研究中国健康志愿者po福辛普利后的药代动力学。方法　10名男性健康受试者po福辛普利20 mg后，用LC/MS/MS法测定不同时间血浆中活性代谢物福辛普利拉浓度，SRM方式选择性检测待测物的特征碎片离子，full-scan ms²方式检测内标物的碎片离子。结果　本法线性良好，精密度、准确度、回收率均符合要求。测得的主要药代动力学参数为：T_1/2=(6.6±1.2) h，　T_max=(3.7±1.1)　h，　C_max=(451.9±251.2)　ng。mL^-1，　AUC_0-∞=(3578.4±2231.2)　h。ng。mL^-1。结论　本实验测得的T_max，C_max和AUC_0-∞均高于文献报道的白人受试者的参数值，而T_1/2显著低于文献值。

PHARMACOKINETIC STUDY OF ORAL FOSINOPRIL IN HEALTHY CHINESE VOLUNTEERS

AIM　To determine the concentration of fosinoprilat in human plasma and study the pharmacokinetics of fosinopril in healthy Chinese male volunteers following a 20 mg oral dose. METHODS　A liquid chromatographic-mass spectrometric assay has been developed for the determination of fosinopilat in plasma of 10 healthy Chinese male subjects orally administered 20 mg fosinopril. Mobile phase: methanol-acetonitrile-0.1% ammonia water (30∶30∶40); Column: Hewlett Packard Zorbax C₈, 5 μm，15 cm×4.6 mm ID; Flow rate: 0.2 ml.min-1. Selected reaction monitoring(SRM) in mass spectrometric method has been used to detect the characteristic ion of fosinoprilat: m/z 434→m/z 237; internal standard substance enalapril was monitored by full-scan ms2: m/z 375→m/z 105～380. RESULTS　Assay linearity was obtained in the range of 5.0～200.0 ng.mL^-1; Intra- and inter-day precisions were lower than 8.9% and 10.1%, respectively; relative error of the method was lower than 12%. Model-independent pharmacokinetic parameters of fosinoprilat were calculated using Topfit 2.0 software. The main pharmacokinetic parameters were: T_1/2=（6.6±1.2）　h，　T_max=(3.7±1.1)　h，　C_max=(451.9±251.2) ng.mL^-1, AUC_0-∞=(3578.4±2231.2) h。ng。mL^-1. The concentration-time curve of fosinoprilat after an oral dose of fosinopril was not fitted to one-, two- or three-compartment model. CONCLUSION　The values of Tmax, Cmax and AUC_0-∞ obtained here were much higher than those reported for Caucasian, but T_1/2 was significantly lower than that reported. These results offered relevant information for rational use of fosinopril in Chinese subjects.