• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.887-903
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• 2008

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.

• CELLMED
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• v.4 no.3
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• pp.17.1-17.8
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• 2014

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.

• Mass Spectrometry Letters
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• v.8 no.4
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• pp.98-104
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• 2017

Ginseng (Panax ginseng Meyer) is a well-known health functional food used as a traditional herbal drug in Asian countries owing to its diverse pharmacological effects. Herb-drug interactions may cause unexpected side effects of co-administered drugs by the alteration of pharmacokinetics through effects on cytochrome P450 activity. In this study, we investigated the herb-drug interactions between Korean red ginseng extract (KRG) and five CYP-specific probes in mice. The pharmacokinetics of KRG extract induced-drug interactions were studied by cassette dosing of five CYP substrates for CYP1A, 2B, 2C, 2D, and 3A and the LC-MS/MS analysis of the blood concentration of metabolites of each of the five probes. The linearity, precision, and accuracy of the quantification method of the five metabolites were successfully confirmed. The plasma concentrations of five metabolites after co-administration of different doses of the KRG extract (0, 0.5, 1, and 2 g/kg) were quantified by LC-MS/MS and dose-dependent pharmacokinetic parameters were determined. The pharmacokinetic parameters of the five metabolites were not significantly altered by the dose of the KRG extract. In conclusion, the single co-administration of KRG extract up to 2 g/kg in vivo did not cause any significant herb-drug interactions linked to the modulation of CYP activity.

• CELLMED
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• v.2 no.2
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• pp.18.1-18.16
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• 2012

An oncology-specific database called OncoRx (http://bit.ly/cancerRx) was previously set up in cyberspace to aid clinicians in identifying interactions of anticancer drugs (ACDs) and chemotherapy regimens with traditional Chinese medicines (TCMs) and complementary and alternative medicines (CAMs). Since then, users have requested the drug-CAM interactions (DCIs) of 5 specific CAMs (cranberry, melatonin, co-enzyme Q10, huachansu, reishi mushroom) to be updated in the database. Pharmacokinetic properties (metabolism, enzyme induction/inhibition, elimination), TCM properties and DCIs of each CAM were collated with 117 ACDs using 9 hardcopy compendia and online databases as resources. Additionally, individual ACDs and CAMs were used as keywords for PubMed searches in combination with the terms 'anticancer drugs', 'drug interactions', 'herb-drug/drug-herb interactions', 'pharmacokinetic interactions' and 'pharmacodynamic interactions'. DCI parameters consisted of interaction effects, evidence summaries, proposed management plans and alternative non-interacting CAMs, together with relevant citations and update dates of the DCIs. OncoRx is also used as a case to introduce the "Four Pharmaco-cybernetic Maxims" of quality, quantity, relationship and manner to developers of digital healthcare tools. Its role in Hayne's "5S" hierarchy of research evidence is also presented. OncoRx is meant to complement existing DCI resources for clinicians and alternative medicine practitioners as an additional drug information resource that provides evidence-based DCI information for ACD-CAM interactions.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.16.1-16.9
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• 2016

Objectives Banha-sasim-tang (BST), which consists of seven different herbs, is one of the most popular herbal formulae for treating gastrointestinal disorders in Eastern Asia. The commonly used herbal medicine is often co-administered with other therapeutic drugs, which raises the possibility of herb-drug interactions and may modify the clinical safety profile of therapeutic drugs. Methods We investigated the potential herb-drug interactions between BST extract and midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC) of MDZ and 1'-hydroxymidazolam (1'-OH-MDZ) was evaluated for both oral and intraperitoneal administration of MDZ, following oral administration of BST (0.5 and 1 g/kg). Results It was found that the AUC of MDZ and 1'-OH-MDZ was lower in case of oral administration of MDZ. Administration of BST extract was not associated with hepatic cytochrome P450 activity. BST extract induced a strong reduction in pH and it has been reported that oral mucosal absorption of MDZ is lower at low pH. The decreased absorption rate of MDZ might be caused by the ingredients of BST and may not be related to other factors such as increased excretion of MDZ by P-glycoprotein. Conclusions The altered pharmacokinetics of midazolam caused by co-administration with BST in vivo could be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.

• Herbal Formula Science
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• v.32 no.3
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• pp.365-375
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• 2024

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.

• The Journal of Korean Medicine
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• v.35 no.2
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• pp.47-59
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• 2014

Objectives: Most drug interactions are attributed to the inhibition or induction of the activity of cytochrome P450s (CYP450). Although the regulation of CYP450s by drugs has been widely reported, there have been few studies on influence of traditional herbal formulas on the drug-metabolizing enzymes. Because herbal formulas have been used traditionally to treat various diseases and because herb-drug interactions are crucial factors determining therapeutic efficacies, a systematic evaluation of the effects of herbal formulas is important. Methods: The effects of Galgeun-tang (GGT, gegen tang), Gumiganghwal-tang (GMGHT, jiuweiqianghuo tang), Insampaedok-san (ISPDS, renshenbaidu powder), Samsoeum (SSE, shensu drink), Socheongryong-tang (SCRT, xiaoqinglong-tang) and Sosiho-tang (SSHT, xiaochaihu tang) that are traditional herbal formulas used to treat common cold, on drug-metabolizing enzymes were evaluated through an in vitro CYP3A4, CYP2D6, CYP2C19 and CYP2E1 inhibition assay to assess its interaction potential with synthetic drugs. The inhibitory effects of herbal formulas were characterized with $IC_{50}$ values. Results: These six herbal formulas inhibited the activities of CYP3A4, 2C19, 2D6 and 2E1, in a concentration-dependent manner. Among the six herbal formulas, GGT critically inhibited CYP2C19, CYP2D6 and CYP2E1. GMGHT also inhibited CYP2D6 and CYP2E1 to a greater extent than the other CYP450 isozymes. Additionally, SSE and SSHT may change the effects of medicines that depend primarily on the CYP2C19 and CYP2E1 pathways. On the other hand, ISPDS and SCRT were not inhibited CYP3A4, CYP2C19, CYP2D6 and CYP2E1-mediated metabolism. Conclusions: These findings provide useful information regarding the safety and effectiveness of herbal formulas.

• Mass Spectrometry Letters
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• v.10 no.2
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• pp.61-65
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• 2019

Korean ginseng (Panax ginseng Meyer) is a traditional herb used across the world to treat various diseases. Although, red ginseng is this herb's most famous product and has demonstrated diverse pharmacological activities, white ginseng (WG) is another ginseng product that is made fresh and individually regulated in Eastern Asia. Red and white ginseng show different characteristics due to distinct processing steps despite originating from the same plant, and the drug interactions induced by WG have not been well documented. Selegiline is a selective monoamine oxidase (MAO) inhibitor used as an antidyskinetic and antiparkinsonian agent. Here we developed a quantification method for selegiline in mouse plasma using a C8 stationary phase in triple quadrupole-mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM). The validated LC-MS/MS method was successfully applied to determine the potential interaction with WG extract (0.1 g/kg/day) pre-administered for 4 weeks. The $AUC_{0-240min}$ of selegiline was altered due to a decrease in the absorption of selegiline with repeated administration of WG extract.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.543-552
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• 2010

The objectives of this study are to examine the current status and problems of herb-drug interaction (HDI) information and information database in Korea and suggest the better way to establish useful HDI database. We collected HDI studies that published in Korea and analyzed according to objective, methods, selection criteria of herbs, number of study, correlation between study subject and frequently used herbal medicine (HM). Then we selected representative HM database on the internet made by Korea Food and Drug Administration (KFDA) among the several databases and analyzed its contents related to HDI. Several HDI studies were carried out from laboratory based research to clinical trials and HM databases have been developed for providing information about different aspects of traditional Korean medicine. But the information of HDI and information database are still far from practical applications because there are no coherence to select study subjects and methods among researchers. So, it is necessary to build up HDI database led by the government for providing systematic HDI information. HDI information database is expected to be able to provide useful evidence for health professionals in prescription and consultation to reduce the chance of adverse effects and improve the quality of medical care.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.3
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• pp.129-137
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• 2012

Objective : Herb-drug interactions have become an important issue because of the consumption of herbal remedies has increased in the world. Yangguksanhaw-tang (Liang ge san huo-tang) and Taeumjowi-tang (Tai yin tiao wei-tang) are typical herbal formulas on Sasang constitution medicine (four-constitution medicine). This study was aimed at evaluating the effects of Yangguksanhaw-tang and Taeumjowi-tang on drug metabolizing enzymes, cytochrome P450 (CYP450) isozymes. Methods : Vivid$^{(R)}$ CYP450 Screening Kits were used to measure of CYP3A4, CYP2C19, CYP2D6 and CYP2E1 activities. This method is based on the use of fluorescent CYP450 substrates that are efficiently metabolized by specific CYP450 isozymes to yield a product with altered fluorescent properties. The percent inhibitions of CYP450s by herbal formulas were calculated. Results : Yangguksanhaw-tang inhibited CYP2C19 and CYP2E1 activities higher than that other CYP450 isozymes. The $IC_{50}$ values of CYP2C19 and CYP2E1 were 159.83 ${\mu}g/mL$ and 261.40 ${\mu}g/mL$, respectively. The CYP2E1 activity was inhibited ($IC_{50}=215.17{\mu}g/mL$) higher than that other CYP450 isozymes by Taeumjowi-tang. Conclusions : These results suggest that Yangguksanhaw-tang may inhibit the metabolism of co-administered drugs whose primary route of metabolism is via CYP2C19 or CYP2E1. Taeumjowi-tang could inhibit the metabolism of co-administered drugs, which are substrates for CYP2E1. Therefore, co-administration of the herbal formulas and other conventional drugs should be undertaken with care.