摘要
目的：建立人血浆和尿液中依拉地平浓度的LC—MS／MS测定法，并用于评价中国健康受试者单次和多次口服依拉地平片的药动学。方法：12例健康受试者单次和多次空腹13服依拉地平片5．0mg，0～48h间隔采集血样，单次给药时，保留0～24h所有尿液。采用LC—MS／MS法测定血浆和尿液依拉地平浓度，DAS2．0软件计算药动学参数。结果：健康受试者单次和多次口服依拉地平片5．0mg的主要药动学参数：Cmax分别为（11．88±3．78）和（10．92±4．31）ng·mL^-1，AUC0-48h分别为（21．4±8．8）和（20．9±9．2）h·ng·mL^-1，Tmax分别为（1．0±0．6）和（0．8±0．5）h，t1/2分别为（8．0±2．4）和（8．2±2．0）h，MRT分别为（4．5±1．9）和（5．2±1．9）h。多次口服依拉地平片后Cav^ss，为（0．84±0．35）ng·mL^-1，DF为（13．5±4．0）。0～24h依拉地平的平均尿药累积排泄率显著小于1．0％。结论：建立的LC—MS／MS法专属性好，灵敏、准确，中国健康受试者单次和多次口服依拉地平片的主要药动学参数无统计学差异，多次给药在体内不存在明显积蓄作用，药动学行为男女无显著差异。
Objective： To establish an LC-MS/MS method for the determination of isradipine in human plasma and urine and study the pharmaeokinetics of isradipine tablets in Chinese healthy volunteers after a single oral dose and multiple doses. Methods： A single oral dose and multiple doses of 5.0 mg isradipine tablets were given to twelve healthy volunteers. Blood samples were collected at predetermined time intervals between 0 - 48 h and urine samples were collected after the single oral dose between 0 - 24 h. Concentrations of isradipine in plasma and urine were determined by LC-MS/MS and the pharmaeokinetic parameters were calculated by DAS 2.0 software. Results ： The main pharmaeokinetie parameters after a single oral dose and multiple doses of 5.0 mg isradipine tablets were as follows： Cmax（11.88 ±3.78） and （10.92±4.31） ng·mL^-1, AUC0-48h（21.4±8.8） and （20.9 ±9.2） h·ng·mL^-1, Tmax（1.0 ±0.6） and （0.8±0.5） h, t1/2（8.0±2.4） and （8.2 ±2.0） h, MRT （4.5 ±1.9） and （5.2 ±1.9） h, respectively. The Cav^ss and DF in multiple doses group were （0.84±0.35） ng·mL^-1 and （ 13.5 ± 4.0） , respectively. The average accumulative excretion rate of isradipine in urine after 24 h was far less than 1.0%. Conclusion： The LC-MS/MS method is specific, sensitive and accurate. There was no significant difference in the pharmacokinetic parameters between the single and multiple oral dose groups. No obvious accumulation effect was observed after multiple oral doses of 5.0 mg isradipine tablets. Gender had no effect on the pharmacokinetic behaviors.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2014年第16期1935-1940,共6页
Chinese Journal of New Drugs
