摘要
目的研究复方利血平氨苯蝶啶中硫酸双肼屈嗪、氨苯蝶啶、氢氯噻嗪及利血平4种有效成分在大鼠体内的药动学。方法SD大鼠随机分为3组,分别单次灌胃给予3.6、10.8和32.4 mg·kg^(-1)复方利血平氨苯蝶啶,不同时间点采血后采用高效液相色谱-质谱(HPLC-MS)测定硫酸双肼屈嗪、氨苯蝶啶、氢氯噻嗪、利血平的血药浓度,并通过DAS软件计算药动学参数。结果单次灌胃给予3.6、10.8和32.4 mg·kg^(-1)复方利血平氨苯蝶啶后,大鼠血浆中硫酸双肼屈嗪的达峰时间(t_(max))分别为1.50、1.33、1.42 h,峰浓度(C max)分别为12.30、38.31、120.52μg·L^(-1);氨苯蝶啶的t_(max)分别为1.33、1.33、1.42 h,C max分别为20.93、67.36、168.64μg·L^(-1);氢氯噻嗪的t_(max)分别为2.00、2.00、1.75 h,C max分别为19.89、57.58、160.78μg·L^(-1);利血平在大鼠血浆中含量极低,仅在32.4 mg·kg^(-1)给药后1和1.5 h检测到微量。结论口服给予大鼠复方利血平氨苯蝶啶后,硫酸双肼屈嗪、氨苯蝶啶和氢氯噻嗪能够较快清除,且其口服吸收基本成线性,在线性范围内给药剂量越大,有效成分的吸收越好。
Objective To study the pharmacokinetics of dihydralazine sulfate,triamterene,hydrochlorothiazide and reserpine in compound reserpine and triamterene in rats.Methods SD rats were randomly divided into three groups.Compound reserpine and triamterene was given at dose of 3.6,10.8 and 32.4 mg·kg^(-1)by single oral gavage,respectively.HPLC-MS was used to measure the blood concentrations of dihydralazine sulfate,triamterene,hydrochlorothiazide,and reserpine at various time points.DAS software was used to compute the pharmacokinetic parameters.Results After a single oral gavage of 3.6,10.8 and 32.4 mg·kg^(-1)of compound reserpine tablets triamterene,the t_(max)of dihydralazine sulfate in rat plasma were 1.50,1.33,and 1.42 h,and the C max of dihydralazine sulfate were 12.30,38.31 and 120.52μg·L^(-1),respectively.The t_(max)of triamterene were 1.33,1.33,and 1.42 h,and the C max of triamterene were 20.93,67.36,and 168.64μg·L^(-1),respectively.The t_(max)of hydrochlorothiazide were 2.00,2.00,and 1.75 h,and the C max of hydrochlorothiazide were 19.89,57.58,and 160.78μg·L^(-1),respectively.Risperdal was found at very low levels in rat plasma,and only trace amounts were detected at 1.00 and 1.50 h of 32.4 mg·kg^(-1)administration.Conclusions Dihydralazine sulfate,triamterene,and hydrochlorothiazide can be eliminated quickly after compound reserpine and triamterene was given orally to rats,and their oral absorption is basically linear.The greater the dosage,the better the absorption of effective components.
作者
谢逸菲
张雯
张森
宋俊科
杨海光
王守宝
吕扬
杜冠华
XIE Yifei;ZHANG Wen;ZHANG Sen;SONG Junke;YANG Haiguang;WANG Shoubao;LYU Yang;DU Guanhua(Beijing Key Laboratory of Drug Targets and Screening Research,Research Center of Polymorphic Drugs,Institute of Materia Medica&Chinese Academy of Medical Sciences,Beijing 100050,China;Beijing Key Laboratory of Polymorphic Drug,Peking Union Medical College,Institute of Materia Medica&Chinese Academy of Medical Sciences,Beijing 100050,China)
出处
《医药导报》
北大核心
2025年第2期183-191,共9页
Herald of Medicine
基金
中国医学科学院医学与健康科技创新工程重大协同创新项目(2021-I2M-1-005)。
关键词
复方利血平氨苯蝶啶
药动学
血药浓度
高效液相色谱-质谱联用
Compound reserpine and triamterene
Pharmacokinetics
Plasma Concentration
High performance liquid chromatography-mass spectrometry
