药物代谢酶和转运体介导的辣椒素-药物相互作用研究进展

秦琰杰, 汪难喜, 张新林, 翟学佳, 吕永宁

中国药学杂志 ›› 2018, Vol. 53 ›› Issue (1) : 1-5.

PDF(1097 KB)
中国药学杂志
PDF(1097 KB)
中国药学杂志 ›› 2018, Vol. 53 ›› Issue (1) : 1-5. DOI: 10.11669/cpj.2018.01.001
综 述

药物代谢酶和转运体介导的辣椒素-药物相互作用研究进展

  • 秦琰杰, 汪难喜, 张新林, 翟学佳, 吕永宁*
作者信息 +

Advances in Metabolizing Enzymes and Transporters Mediated Capsaicin-Drug Interaction

  • QIN Yan-jie, WANG Nan-xi, ZHANG Xin-lin, ZHAI Xue-jia, LÜ Yong-ning*
Author information +
文章历史 +

摘要

随着辣椒素的临床研究不断深入,辣椒素-药物相互作用问题日益凸显。近年来的研究结果显示,辣椒素对多种药物代谢酶和转运体有显著的诱导或抑制作用,通过多种因素影响合用药物的体内过程,进而导致复杂的药物相互作用的发生。笔者查阅了近几年国内外相关研究,从辣椒素对药物代谢酶及转运体的调控作用等方面进行综述,预测可能与辣椒素发生显著相互作用的药物,以期为临床合理用药提供理论指导,同时为复杂的药物相互作用提供新的研究思路。

Abstract

With the continuously clinical study of capsaicin, capsaicin-drug interaction has become increasingly prominent. In recent years, the studies indicate that capsaicin shows a significant inducing or inhibitory effect on a variety of drug metabolism enzymes and transporters, thereby leading to the occurrence of complex drug interactions and affecting the other drugs in vivo process. In this paper, the modulation effect of capsaicin on drug metabolizing enzymes and transporters by reviewing the relevant research at home and abroad in recent years were summarized, and the drug-drug interactions associated with capsaicin in order to provide theoretical guidance for clinical rational drug use were explored . Furthermore, complex drug-drug interaction studies can be provided with prior examples.

关键词

辣椒素 / 药物代谢酶 / 转运体 / 调控作用 / 药物-药物相互作用

Key words

capsaicin / drug-metabolizing enzymes / transporters / regulation / drug-drug interactions

引用本文

EndNote

Ris (Procite)

Bibtex

导出引用
秦琰杰, 汪难喜, 张新林, 翟学佳, 吕永宁. 药物代谢酶和转运体介导的辣椒素-药物相互作用研究进展[J]. 中国药学杂志, 2018, 53(1): 1-5 https://doi.org/10.11669/cpj.2018.01.001
QIN Yan-jie, WANG Nan-xi, ZHANG Xin-lin, ZHAI Xue-jia, LÜ Yong-ning. Advances in Metabolizing Enzymes and Transporters Mediated Capsaicin-Drug Interaction[J]. Chinese Pharmaceutical Journal, 2018, 53(1): 1-5 https://doi.org/10.11669/cpj.2018.01.001
中图分类号： R965   

参考文献

[1] VIRUS R M, GEBHART G F. Pharmacologic actions of capsaicin: apparent involvement of substance P and serotonin[J]. Life Sci, 1979, 25(15):1273-1283.
[2] SRINIVASAN K. Biological activities of red pepper (Capsicum annuum) and its pungent principle capsaicin:a review[J]. Crit Rev Food Sci Nutr, 2016, 56(9):1-53.
[3] ZHOU S, GAO Y, JIANG W, et al. Interactions of herbs with cytochrome P450[J]. Drug Metab Rev, 2003, 35(1):35-98.
[4] REILLY C A, EHLHARDT W J, JACKSON D A, et al. Metabolism of capsaicin by cytochrome P450 produces novel dehydrogenated metabolites and decreases cytotoxicity to lung and liver cells[J]. Chem Res Toxicol, 2003, 16(3):336-349.
[5] LADDA M A, GORALSKI K B. The effects of CKD on cytochrome P450-mediated drug metabolism[J]. Adv Chronic Kidney Dis, 2016, 23(2):67-75.
[6] HALVORSON M, GREENWAY D, EBERHART D, et al. Reconstitution of testosterone oxidation by purified rat cytochrome P450p (ⅢA 1)[J]. Arch Biochem Biophys, 1990, 277(1):166-180.
[7] SHU Z, ZHAI X, LIU J, et al. Effects of capsaicin on rat cytochrome P450 isoforms by cocktail probe drug method [J]. China Pharm(中国药师), 2014, 17(10): 1613-1618.
[8] BABBA S, CHANDA S, BLEY K. Inhibition and induction of human cytochrome P450 enzymes in vitro by capsaicin[J]. Xenobiotica, 2010, 40(12):807-816.
[9] ZHANG Q H, HU J P, WANG B L, et al. Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo[J]. J Asian Nat Prod Res(亚洲天然产物研究), 2012, 14(4):382-395.
[10] TAKANOHASHI T, ISAKA M, UBUKATA K, et al. Studies of the toxicological potential of capsinoids, XIII: inhibitory effects of capsaicin and capsinoids on cytochrome P450 3A4 in human liver microsomes [J]. Int J Toxicol, 2010, 29(S2):22-26.
[11] SURH Y J, LEE S S. Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential[J]. Life Sci, 1995, 56(22):1845-1855.
[12] ZHANG Q H, LI E, WANG B L, et al. Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities [C]. Wuhan:National Conference on Drug and Chemical Metabolism, 2009.
[13] ZHANG Z, HAMILTON S M, STEWART C. Inhibition of liver microsomal cytochrome P450 activity and metabolism of the tobacco-specific nitrosamine NNK by capsaicin and ellagic acid[J]. Anticancer Res, 1993, 13(6):2341-2346.
[14] HAN E H, HWANG Y P, KIM H G, et al. CCAAT/ enhancer-binding protein β activation by capsaicin contributes to the regulation of CYP1A1 expression, mediated by the aryl hydrocarbon receptor[J]. Br J Pharmacol, 2011, 164(6):1600-1613.
[15] DIPPLE A. Reactions of polycyclic aromatic hydrocarbons with DNA[J]. Iarc Sci Publ, 1994, (125):107-129.
[16] KLEES T M, SHEFFELS P, DALE O, et al. Metabolism of alfentanil by cytochrome p4503a (cyp3a) enzymes[J]. Drug Metab Dispos, 2005, 33(3):303-311.
[17] DESTA Z, KERBUSCH T F, LOCKHART D A. Effect of clarithromycin on the pharmacokinetics and pharmacodynamics of pimozide in healthy poor and extensive metabolizers of cytochrome P450 2D6 (CYP2D6)[J]. Clin Pharmacol Ther, 1999, 65(1):10-20 .
[18] JÖNSSON G, ASTRÖM A, ANDERSSON P. Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver [J]. Drug Metab Dispos, 1995, 23(1):137-142.
[19] EVANS D C, O′CONNOR D, LAKE B G, et al. Eletriptan metabolism by human hepatic CYP450 enzymes and transport by human P-glycoprotein[J]. Drug Metab Dispos, 2003, 31(7):861-869.
[20] ZHU H D, GU N, WANG M, et al. Effects of capsicine on rat cytochrome P450 isoforms CYP1A2, CYP2C19 and CYP3A4[J]. Drug Dev Ind Pharm, 2015, 41(11):1-5.
[21] XU B B, ZHENG S L, ZHU H D. Evaluation of drugs pharmacokinetic parameters related to enzymatic effects of capsaicin[J]. Lat Am J Pharm, 2014, 33(1):129-134.
[22] LIU J M, SHU Z, SHI F, et al. Simultaneous evaluation of the effect of capsaicin on the activities of CYP1A2, 2C11 and 3A by cocktail probe drug method [J]. Chin Pharm J(中国药学杂志), 2013, 48(7):553-557.
[23] KATO R, HIGASHITANI A, IRIE T, et al. Influence of capsaicin on fluctuation of digoxin pharmacokinetics in lipopolysaccharide-treated rats[J]. Xenobiotica, 2012, 42(8):798-807.
[24] ZHAI X J, CHEN J G, LIU J M, et al. Food-drug interactions: effect of capsaicin on the pharmacokinetics of simvastatin and its active metabolite in rats[J]. Food Chem Toxicol, 2013, 53: 168-173.
[25] ZHAI X J, LU Y N. Food-drug interactions: effect of capsaicin on the pharmacokinetics of galantamine in rats[J]. Xenobiotica, 2012, 42(11):1151-1155.
[26] DONG R H, FANG Z Z, ZHU L L, et al. Investigation of UDP-glucuronosyltransferases (UGTs) inhibitory properties of carvacrol[J]. Phytother Res, 2012, 26(1):86-90.
[27] FISHER M B, PAINE M F, STRELEVITZ T J, et al. The role of hepatic and extrahepatic UDP-glucuronosyltransferases in human drug metabolism[J]. Drug Metab Rev, 2001, 33(3-4):273-297.
[28] ZHU C R, ZHAI X J, CHEN F, et al. Capsaicin induces metabolism of simvasatin in rat: involvement of upregulating expression of Ugt1a1[J]. Die Pharmazie, 2016, 71(5):269-273.
[29] RUSSEL F G M. Transporters: Importance in Drug Absorption, Distribution, and Removal[M]. Enzyme-and Transporter-Based Drug-Drug Interactions.New York:Springer, 2010: 27-49.
[30] DAOOD M J, TSAI C, AHDABBARMADA M, et al. ABC Transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS [J]. Neuropediatrics, 2008, 39(4):211-218.
[31] OOSTENDORP R L, BUCKLE T, BEIJNEN J H, et al. The effect of P-gp (Mdr1a/1b), BCRP (Bcrp1) and P-gp/BCRP inhibitors on the in vivo absorption, distribution, metabolism and excretion of imatinib[J]. Invest New Drugs, 2009, 27(1):31-40.
[32] NEUHOFF S, YEO K R, BARTER Z, et al. Application of permeability-limited physiologically-based pharmacokinetic models: part Ⅱ-prediction of P-glycoprotein mediated drug-drug interactions with digoxin[J]. J Pharm Sci,2014, 102(9):3161-3173.
[33] HILDEBRAND J L, BAINS O S, LEE D S H, et al. Functional and energetic characterization of P-gp-mediated doxorubicin transport in rainbow trout (Oncorhynchus mykiss) hepatocytes[J]. Comp Biochem Physiol C Toxicol Pharmacol, 2009, 149(1):65-72.
[34] DEAN M, RZHETSKY A, ALLIKMETS R. The human ATP-binding cassette (ABC) transporter superfamily[J]. Genome Res, 2001, 11(7):1156-1166.
[35] LIANG Q, DUAN L, ZHUANG Z, et al. Effect of capsaicin on intestinal permeation of P-glycoprotein substrate rhodamine 123 and fluorescein sodium in rats[J]. J South Med Univ J South Med Univ(南方医科大学学报), 2015,35(5):724-727.
[36] NABEKURA T K, KITAGAWA S. Effects of dietary chemopreventive phytochemicals on p-glycoprotein function[J]. Biochem Biophys Res Commun, 2005, 327(3):866-870.
[37] HAN Y, TAN T M, LIM L Y. Effects of capsaicin on P-gp function and expression in Caco-2 cells[J]. Biochem Pharmacol, 2006, 71(12):1727-1734.
[38] BEDADA S K, APPANI R, BOGA P K, et al. Capsaicin pretreatment enhanced the bioavailability of fexofenadine in rats by polycoprotein modulation: in vitro, in situ and in vivo evaluation[J]. Drug Dev Ind Pharm, 2017, 43(6):932-938.
[39] ZHAI X J, SHI F, CHEN F, et al. Capsaicin pretreatment increased the bioavailability of cyclosporin in rats: involvement of P-glycoprotein and CYP 3A inhibition [J]. Food Chem Toxicol, 2013, 62(12):323-328.
[40] NIEMI M, PASANEN M K, NEUVONEN P J. Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake[J]. Pharmacol Rev, 2011, 63(1):157-181.
[41] CHEN F. The effects and mechanism of capsaicin on Oatp1b2 and Bcrp mediated transport of pitavastatin and sulfasalazine in rats [D]. Wuhan:Huazhong University of Science and Technology, 2015.
[42] ROWLAND M, PECK C, TUCKER G. Physiologically-based pharmacokinetics in drug development and regulatory science[J]. Annu Rev Pharmacol Toxicol, 2011, 51(1):45-73.

基金

国家自然科学基金面上项目(81473287,81673715)
PDF(1097 KB)

Accesses

Citation

Detail
段落导航
相关文章

/

〈 〉