와파린과 생약제의 약물 상호작용 리뷰

천부순,김종윤,김정태,구본기,유기연 한국병원약사회 2013 病院藥師會誌 Vol.30 No.5

Objectives: Concerns on drug interaction with herbal preparations are increasing as herbs are becoming more widely used as dietary supplements. Drug-herb interactions can alter therapeutic effects on patients, particularly in medications with narrow therapeutic index (NTI),such as warfarin. However, the potential risks from drug-herb interactions are often ignored or underestimated even when known. As there is limited documented information on potential herb-drug interactions, it is essential to provide clinical practices with the updated information as well as the mechanism on potential herb-drug interactions. The goals of this article are: (1) To review the evidence-based data and biomedical reports on herb-warfarin interactions in humans,and (2) To further provide the documented mechanisms and consequences of drug-herb interactions Methods: PubMed was used to search the clinical trials and the case reports on herb-warfarin interactions in humans. This article focused on the data conducted in humans as well as the studies in animal models, in vitro, in vivo are cited, where relevant. Results: There are several mechanisms for the occurrence of herb-drug interactions. Herbs which may affect warfarin therapy include the following: green tea, black tea, chamomile, cranberry,danshen, dong quai, ginseng, lyceum, noni, pomegranate, and St John’s wort. A vast majority of clinically significant PK herb-drug interactions involve cytochrome P450 (CYP)enzymes, UDP-glucuronosyltransferases (UGT), and drug transporters. Conclusion: The reported effects of herbs on warfarin are contradictory. Clinical effects of herbdrug interactions depend on different factors, such as genotypes of patients, origins and constituents of herbs, and doses of administered drugs. Hence, further controlled clinical studies in humans are needed in order to verify the potential herbal interactions with conventional drugs.

암 환자의 한약-양약 상호작용에 대한 고찰

방선휘,한성수,조정효,이연월,조종관,유화승,Bang, Sun-Hwi,Han, Sung-Su,Cho, Jung-Hyo,Lee, Yeon-Weol,Cho, Chong-Kwan,Yoo, Hwa-Seung 대한한방내과학회 2008 大韓韓方內科學會誌 Vol.29 No.4

Objectives : We present some opinions to reduce the risk of herb-drug interactions through scanning "About Herbs" of the Memorial Sloan Kettering Cancer Center Website. Methods : We searched the Memorial Sloan Kettering Cancer Center Website of About Herbs and investigated herb-drug interactions. Results : There are 237 herbs and 196 drugs on About Herbs. 81.1% of herbs have fewer than 2 interactions listed.: 86.3% of drugs fewer than 3 interactions. Especially, 13 herbs were reported to have interactions with inclusive chemoagents on About Herbs. Only L-theanine has positive interaction with inclusive chemoagents. The others have negative interactions with inclusive chemoagents. 12 single chemoagents were reported to have interactions with some herbs. Especially tamoxifen-black cohosh, methotrexate-glutamin and aldesleukin-Huang Chi have positive interactions to increase the effects of the chemoagent. Conclusions : We should urgently create a risk management system of herb-drug interactions and take note of the risk of herb-drug interactions. We should build up systemic, evidence-based informations on popular herbs used by Korean cancer patients and herb-drug interactions in oncology like About Herbs.

Evaluation of Metabolism-Mediated Herb-Drug Interactions

나동희,Hye Young Ji,박은지,Myung Sun Kim,Kwang-Hyeon Liu,이혜숙 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.11

As the use of herbal medicines increases, the public health consequences of drug-herb interactions are becoming more significant. Herbal medicines share the same drug metabolizing enzymes and drug transporters, including cytochrome P450 enzymes (CYPs), glucuronosyltransferases (UGTs), and P-glycoprotein, with several clinically important drugs. Interactions of several commonly used herbal medicines, such as Ginko biloba, milk thistle, and St. John’s wort, with therapeutic drugs including warfarin, midazolam, alprazolam, indinavir, saquinavir, digoxin, nifedipine, cyclosporine, tacrolimus, irinotecan, and imatinib in humans have been reported. Many of these drugs have very narrow therapeutic indices. As the herb-drug interactions can significantly alter pharmacokinetic and pharmacodynamic properties of administered drugs, the drugs interacting with herbal medicines should be identified by appropriate in vitro and in vivo methods. A good understanding of the mechanisms of herb-drug interactions is also essential for assessing and minimizing clinical risks. In vitro methods are useful for providing mechanistic information and evaluating multiple components in herbal medicines. This review describes major factors affecting the metabolism of herbal medicines, mechanisms of herb-drug interactions mediated by CYPs and UGTs, and several in vitro methods to assess the herb-drug interactions. Finally, drug interactions of Ginkgo biloba and St. John’s wort, as representative herbal medicines, are described.

단미 한약과 합성 혈압약의 상호작용

오유나 ( Yoona Oh ),이홍범 ( Hongbum Lee ),김형우 ( Hyungwoo Kim ) 대한본초학회 2018 大韓本草學會誌 Vol.33 No.6

Objective : Many patients take antihypertensive drugs as well as herbal medicines at the same time in order to treat other symptoms or to keep their well-being. In this study, interactions between herbal medicines and synthetic antihypertensive drugs were analyzed. Methods : To investigate the interaction between herbal medicines and synthetic antihypertensive drugs, three electronic databases, including OASIS, Mediline and Sciencedirect were searched. Experimental and clinical studies on the interaction between herbal medicines and antihypertensive drugs were independently reviewed and included. Results : Analyzing selected studies, twenty herbs were found to interact with antihypertensive drugs. Herbs found to increase the antihypertensive effect were Panax ginseng, Carthamus tinctorius, Magnolia officinalis, Silybum marianum, Scutellaria baicalensis, Schisandra chinensis, Sophora flavescens, Piper nigrum, Curcuma longa, Ginkgo biloba, Juncus effuses and Hydrastis canadensis . In contrast, Commiphora myrrha, Rhodiola rosea, Hypericum perforatum, Eurycoma longifolia, and Daturae metel were found to inhibit the antihypertensive effect. Stephania tetrandra could increase or decrease the effect depending on the type of antihypertensive drug. Epedria sínica was suspected of pharmacodynamic interaction with antihypertensive drug. Glycyrrhiza uralensis has been reported to have serious side effects in combination with antihypertensive drugs. Conclusion : These results imply that when used in combination with herbal medicines and synthetic antihypertensive drugs, proper doses and herbs which are to avoid need to be informed to the patients. Despite concerns about interactions between herbal medicines and synthetic drugs, related research is very limited. More systematic researches are needed to give information on patient safety as well as to guide clinical practice.

한국인의 일반 · 전문의약품-한약제제 병용 처방 실태분석 및 잠재적 상호작용 고찰

박상준(Sang-Jun Park),오인선(In-Sun Oh),박민정(Minjung Park),장보형(Bo-Hyoung Jang),신주영(Ju-Young Shin) 대한약학회 2022 약학회지 Vol.66 No.2

Herbal medicines have gained a reputation for being efficacious and safe over hundreds of years. Nowadays, people are easily exposed to drugs and herbal medications concurrently. Therefore, it is essential for regulatory authorities and physicians to closely monitor potential herb-drug interactions. The aim of this study was to determine (1) the prevalence of the concurrent use of drugs and herbal medications, (2) demographic and clinical characteristics of concurrent users, (3) risk factors associated with concurrent use, (4) prescription patterns, and (5) potential herb-drug interactions by using a nationwide insurance claims database. We included patients with herbal medicine records in 2010- 2015 from the National Health Insurance Service-National Sample Cohort 2.0. The herbal medicine users were divided into two groups: concurrent users who were prescribed both herbal and drug medications simultaneously and non-concurrent users. The proportion of concurrent use increased steadily from 2.5% in 2010 to 5.2% in 2015, and the growth rate in the elderly population aged 60-79 years was the highest, from 0.7% in 2010 to 2.8% in 2015. Concurrent users in 2015 were prone to be female; old; and have chronic diseases including hypertension (adjusted odds ratio [aOR], 4.89; 95% CI, 4.54-5.27), hyperlipidemia (aOR, 2.01; 1.89-2.14), and diabetes (aOR, 1.81; 1.67-1.98). The most common concurrently used combinations were Gunghatang-aspirin, Ojeoksan-aspirin, and Ojeoksan-atorvastatin. In this study, we investigated the herb-drug combinations that are used concurrently and related characteristics and elucidated the factors related to the concurrent use and the most common concurrently used herb-drug combinations.

HS-23, a standardized extract of the dried flower buds of Lonicera japonica, has no major impact on drug transporters and on the pharmacokinetics of ceftriaxone and levofloxacin in rats

김주현,권미화,권순상,김영목,홍성운,연성흠,송임숙,이혜숙 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.1

Concurrent administration of herbal drugs that modulate drug transporter activities can cause herb–drug interactions in the process of the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. For this reason, regulatory agencies have instituted guidelines for the investigation of potential herb–drug interactions during the drug development process. Therefore, the purpose of this study was to investigate the herb–drug interaction potential of HS-23, an extract of the dried flower buds of Lonicera japonica, which is being evaluated for use in the treatment of sepsis in a phase II clinical study. The inhibitory effects of HS-23 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 and LLC-PK1 cells. The effects of HS-23 on the pharmacokinetics of ceftriaxone and levofloxacin, common combination drugs for sepsis treatment were also examined in rats.HS-23 (up to 100 lg/mL) did not inhibit the in vitro transport activities ofOCT1/2,OAT1/ 3, OATP1B1/1B3, P-gp, and BCRP or the pharmacokinetics of ceftriaxone and levofloxacin in vivo after a single intravenous dose of 40 mg/kg. In conclusion, HS-23 may not have significant herb–drug interactions with the prevalently used ceftriaxone and levofloxacin, in rats even at its effective dose.

Drug-herb interactions: Mechanisms involved and clinical implications of five commonly and traditionally used herbs

Chin Eng Ong,Yan Pan 셀메드 세포교정의약학회 2014 셀메드 (CellMed) Vol.4 No.3

Herbal remedies are commonly used by patients worldwide. Because these herbal preparations share the same metabolic and transport proteins with prescribed medicines, the potential for a drug-herb interaction is substantial and is an issue of significant concern. This review paper summarizes drug-herb interactions involving inhibition or induction of cytochrome P450 enzymes, drug transporters as well as modulation of drug pharmacodynamics. An increasing number of in vitro and animal studies, case reports and clinical trials evaluating such interactions have been reported, and implications of these studies are discussed in this review. The most commonly implicated drugs in the interaction include anticoagulants, antiplatelets, immunosuppressants, anti-neoplastics, protease inhibitors, and some antidepressants. Pharmacokinetic and/or pharmacodynamic interactions of five commonly used herbal remedies (danshen, garlic, Ginkgo biloba, ginseng, and St John’s wort) with these drugs are presented, with focus of discussion being the potentials for interaction, their mechanisms and clinical implications. There is a necessity for adequate pharmacovigilance to be carried out in minimizing unanticipated but often preventable drug-herb interactions.

PubMed 수록 논문을 활용한 한약 처방과 양약 상호작용에 관한 연구 동향 분석

예상준 대한한의학방제학회 2024 大韓韓醫學方劑學會誌 Vol.32 No.3

Objectives : Herbal formula consist of multiple herbs, which can potentially interact with conventional drugs. If these interactions are not properly understood, they may reduce treatment efficacy or cause unexpected side effects. Thus, this study collected and analyzed papers on herbal formula and conventional drug interactions from PubMed to analyze various research trends. Methods : To analyze research trends on herbal formula and drug interactions, we first created search queries using a dictionary of herbal formula terms and collected related papers from PubMed using the Entrez API. The PubTator API was applied to identify compound names in the abstracts, recognizing compounds registered in the DrugBank as conventional drugs. Sentences describing interactions between herbal formulas and drugs were extracted using pattern matching, and relevant papers were selected. Trends were then analyzed by year, country, major formulas, major drugs, and interaction networks. Results : Yearly analysis showed a gradual increase in paper counts with a significant rise after 2010. Country analysis revealed that China published the most papers (53), followed by Japan (19) and South Korea (8). formula analysis identified 'sosiho-tang' and 'siryung-tang' as the most frequently mentioned (7 times each). Drug analysis showed '5-fluorouracil', 'acetaminophen', 'entecavir', and 'streptozotocin' were the most frequently mentioned (4 times each). Network analysis revealed 'sosiho-tang and tolbutamide' and 'siryung-tang and prednisolone' as the most frequently mentioned interactions (3 times each). Disease analysis indicated 'urogenital diseases' were the most discussed (32 mentions), followed by 'pathological conditions, signs, and symptoms' and 'digestive system diseases' (25 mentions each). Conclusions : Analyzing research trends on herbal formula and conventional drug interactions provides basic data for subsequent research, aiming to reduce side effects and enhance treatment efficacy in clinical settings.

Interactions of ginseng with therapeutic drugs

Min‑Koo Choi,Im‑Sook Song 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.10

Ginseng is the most frequently used herbalmedicine for immune system stimulation and as an adjuvantwith prescribed drugs owing to its numerous pharmacologicactivities. It is important to investigate the beneficialeffects and interaction of ginseng with therapeutic drugs. This review comprehensively discusses drug metabolizingenzyme- and transporter-mediated ginseng–drug interactionby analyzing in vitro and clinical results with a focus onginsenoside, a pharmacologically active marker of ginseng. Impact of ginseng therapy or ginseng combination therapyon diabetic patients and of ginseng interaction with antiplateletsand anticoagulants were evaluated based on ginsengorigin and ginsenoside content. Daily administration ofKorean red ginseng (0.5–3 g extract; dried ginseng > 60%)did not cause significant herb–drug interaction with drugmetabolizing enzymes and transporters. Among varioustherapeutic drugs administered in combination with ginseng,adjuvant chemotherapy, comprising ginseng (1–3 gextract) and anticancer drugs, was effective for reducingcancer-related fatigue and improving the quality of life andemotional scores. Limited information regarding ginsenosidecontent in each ginseng product and plasma ginsenosideconcentration among patients necessitates standardizationof ginseng product and establishment of pharmacokinetic–pharmacodynamic correlation to further understand beneficialeffects of ginseng–therapeutic drug interactions in futureclinical studies.

항혈소판약물과 생약제의 상호작용: 리뷰

천부순,김종윤,김정태,유기연 한국병원약사회 2014 病院藥師會誌 Vol.31 No.2

Objectives : Antiplatelet agents are commonly used worldwide for the prevention ofcardiovascular or cerebrovascular diseases by inhibiting platelet aggregation and thrombus formation. As the herbal medicine and crude drug market is gradually expanding with increasedpopularity, drug-herb interaction has become a rising topic. The most frequently interactingdrugs with herbs were reported to be antiplatelet agents and anticoagulants. The purpose of thisresearch is to focus on the interactions in antiplatelet agents with herbal medicines in order topresent safe use of these agents, including aspirin or clopidogrel, along with the effective use ofCAM (Complementary and Alternative Medicine). Methods : This research includes literatures on only the clinical results of drug interactions, primarilyassembled from PubMed and additionally from MedlinePlus Drugs and Supplements Directory, Martindale, Natural Standard, BNF, Stockely’s Herbal Medicines, etc. Results : Herbs that resulted in teractions with an antiplatelet agent were as follows : aloe vera,garlic, ginger, ginkgo, ginseng, and St. John’s wort. The results were all clinical and had morethan one case. Studies on garlic, ginger, and ginkgo were conducted on healthy adult subjectswhereas the clinical study on St. John’s wort was conducted on patients with stent placed ontheir coronary artery. Conclusions : Although clinical studies and cases on drug-herb interaction had varied results, theresults could lead to the conclusion that many herbal medicines will have interactions withantiplatelet agents. Therefore, potential interactions should be considered when simultaneouslyusing herbal medicine and conventional medicine prior to treatment. Further research using alarger population is required for more accurate results.