毛喉鞘蕊花提取物福司可林的体外代谢研究  

In vitro metabolism of forscolin isolated from Coleus forskohlii

作　　者：张曼[1,2] 孟志云[2] 朱晓霞[2] 窦桂芳[2] 

机构地区：[1]中南大学药学院,湖南长沙410013 [2]军事医学科学院野战输血研究所,北京100850

出　　处：《药学学报》2013年第3期383-389,共7页Acta Pharmaceutica Sinica

基　　金：国家重大新药创制科技重大专项资助项目(1009ZX909304-004)

摘　　要：研究福司可林在血浆和肝微粒体中的代谢性质,为临床合理用药提供参考。采用HPLC-MS/MS的检测方法,通过测定福司可林的浓度,考察福司可林在大鼠、比格犬、猕猴和人4个不同种属肝微粒体中的代谢稳定性,鉴定福司可林在人肝微粒体中代谢的主要参与酶以及对人肝微粒体中细胞色素P450(cytochrome P450,CYP450)各亚型酶的抑制作用。结果表明,福司可林在大鼠、比格犬、猕猴和人4个种属血浆中均不代谢;在4个种属肝微粒体中均有不同程度的代谢,其t1/2分别为(52.0±15.0)、(51.2±5.9)、(6.0±0.2)、(11.9±1.8)min;CLint分别为(75.6±18.7)、(60.9±6.8)、(513.8±14.3)、(176.2±25.6)mL.min 1.kg 1;CL分别为(34.8±4.5)、(23.3±1.0)、(40.3±0.5)、(17.9±0.3)mL.min 1.kg 1。在人肝微粒体中福司可林主要被CYP3A4代谢;福司可林在浓度为0.1 ng.mL 1～5μg.mL 1内,对人肝微粒体中CYP3A4存在竞争性抑制作用。可见,福司可林在肝微粒体中代谢消除较快,在临床上与其他被CYP3A4代谢的药物合用时应注意药物相互作用。This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The tl/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were （52.0 士 15.0）, （51.2士5.9）, （6.0士0.2） and （11.9士1.8） min; CLint were （75.6士18.7）, （60.9士6.8）, （513.8士14.3） and （176.2士25.6） mL＇min l.kg 士; CL were （34.8士4.5）, （23.3士 1.0）, （40.3士0.5） and （17.9士0.3） mL-min l.kg l, respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng＇mL1 and 5 mL-1. Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.

关 键 词：福司可林 肝微粒体 代谢表型 

分 类 号：R969[医药卫生—药理学]