In Vitro Assessment of CYP-Mediated Drug Interactions for Kinsenoside, an Antihyperlipidemic Candidate.
Kinsenoside, the herb-derived medicine isolated from the plant Anoect chilus, has diverse pharmacological actions, and it is considered to be a promising antihyperlipidemic drug candidate. This study evaluates the effects of kinsenoside on CYP enzyme-mediated drug metabolism in order to predict the potential for kinsenoside-drug interactions. Kinsenoside was tested at different concentrations of 0.1, 0.3, 1, 3, 10, 30, and 100 µM in human liver microsomes. The c Cktail probe assay based on liquid chromatography-tandem mass spectrometry was conducted to measure the CYP inhibitory effect of kinsenoside. Subsequently, the metabolism profiles of amlodipine and lovastatin in human liver microsomes were analyzed following co-incubation with kinsenoside. The concentration levels of the parent drug and the major metabolites were compared with the kinsenoside-cotreated samples. The effect of kinsenoside was negligible on the enzyme activity of all the CYP isozymes tested even though CYP2A6 was slightly inhibited at higher concentrations. The drug-drug interaction assay also showed that the concomitant use of kinsenoside has a non-significant effect on the concentration of lovastatin or amlodipine, and their major metabolites. So, it was concluded that there is almost no risk of drug interaction between kinsenoside and CYP drug substrates via CYP inhibition.
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan Gyeonggi-do 426-791, Korea. dr.shaheedmarwat@yahoo.com.
Shaheed Ur
SU
Rehman
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan Gyeonggi-do 426-791, Korea. chm2456@hanyang.ac.kr.
Min Sun
MS
Choi
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan Gyeonggi-do 426-791, Korea. kis@hanyang.ac.kr.
In Sook
IS
Kim
School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. luozengwei@hust.edu.cn.
Zengwei
Z
Luo
School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. yongboxue@mail.hust.edu.cn.
Yongbo
Y
Xue
School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. gyap@hust.edu.cn.
Guangming
G
Yao
School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. zhangyh@mails.tjmu.edu.cn.
Yonghui
Y
Zhang
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan Gyeonggi-do 426-791, Korea. yoohh@hanyang.ac.kr.
Hye Hyun
HH
Yoo
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D017311:Amlodipine / Q000378:metabolism / Q000494:pharmacology; D002853:Chromatography, Liquid; D065637:Cytochrome P-450 CYP2A6 / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology*; D008658:Inactivation, Metabolic / Q000187:drug effects / Q000235:genetics*; D008148:Lovastatin / Q000378:metabolism / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009005:Monosaccharides / Q000737:chemistry / Q000494:pharmacology*; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry
C422363:3-glucopyranosyloxybutanolide; D065607:Cytochrome P-450 Enzyme Inhibitors; D000960:Hypolipidemic Agents; D009005:Monosaccharides; D017311:Amlodipine; D003577:Cytochrome P-450 Enzyme System; D008148:Lovastatin; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D015107:4-Butyrolactone
CYP inhibition; drug interactions; human liver microsomes; kinsenoside