中药注射剂对细胞色素P450的调控与药物相互作用预测

近年来中药注射剂在临床上应用广泛,与其他药物联合应用极为普遍,联合用药是否会产生细胞色素P450（CYP）酶介导的代谢性药物相互作用,从而影响疗效和用药安全,已越来越受到关注.本文就近年来中药注射剂对CYP酶影响的国内外研究进行了综述,按各亚型酶进行归类,归纳了中药注射剂对CYP各亚型酶的作用（诱导、抑制）,以预测中药注射剂及与哪些药物联合应用时可能会产生潜在的代谢性药物相互作用,与哪些药物可安全联用,从而为临床安全合理用药及相关研究提供参考,保障患者用药安全有效,规避用药风险.     

中草药与西药相互作用的机制探讨

目的探讨中药与西药联用的相互作用,促进中药的合理、安全使用。方法通过检索近年来文献,归纳研究方法、相互作用机制,从中西药配伍、药效学及药动学方面对中西药物相互作用进行探讨。结果中西药物合用,药物之间可能因为配伍禁忌、药理协同、拮抗、相关代谢酶的被诱导或抑制,导致疗效的改变,增加或减少不良反应,甚至发生毒性反应。结论应加强中西药相互作用的研究。     

细胞色素P450酶介导的中药注射剂代谢性相互作用研究现状及思考

中药注射剂因药物相互作用引起的不良反应问题日益凸显,而细胞色素P450（CYP450）酶是影响药物体内处置过程的重要因素,其表达和功能的改变常常引起药动学的变化,是代谢性药物相互作用的主要靶点。因此,开展中药注射剂与化学药的药物相互作用研究十分必要,就CYP450酶介导的中药注射剂与化学药相互作用的研究现状以及常见的中药注射剂对CYP450酶影响的研究进行综述,为中药注射剂的临床应用和相互作用研究提供参考。     

化学药物与中药相关的药物相互作用

目的：综述文献报道的有关中药与化学药品的相互作用。方法：检索Medline和中国药学文摘。结果：多种中药和天然植物可以通过抑制或诱导药物代谢酶，影响化学药品的代谢，发生相互作用，一些中药还可以与化学药品发生药效学相互作用，引起药物不良反应。结论：中药的药物动力学、代谢催化机制、中药与化学药品相互作用等值得深入研究。     

中药有效成分血浆蛋白结合率的研究进展与相关规律探讨

目的系统了解中药有效成分血浆蛋白结合率国内外研究进展,并探讨相关规律,为相关研究提供借鉴和参考,并为预测中药与其他药物联用时,是否会发生血浆蛋白结合介导的药物相互作用提供依据。方法通过文献检索,对中药有效成分血浆蛋白结合率的相关报道进行分析和总结。结果中药有效成分血浆蛋白结合率的研究国内外已有较多报道,显示不同结构的成分血浆蛋白结合率有较大差异,与结构类别、官能团位置、官能团数量等因素有关,且呈现一定的规律性。结论很多中药成分具有较高的血浆蛋白结合率,这些中药及其制剂与高血浆蛋白结合率的药物联用时,应关注可能会因为竞争血浆蛋白结合而产生药物相互作用,以保障患者用药安全。     

浅析中药注射液不良反应发生原因和应对措施

目的分析中药注射液不良反应发生的原因和应对措施,以促进临床合理用药。方法根据相关文献对中药注射液不良反应发生的原因和应对措施进行总结。结果诱发中药注射液不良反应的因素有个体差异、药物因素、药物的相互作用、给药方法、原材料和制作工艺等。结论在临床和生产上都要加强对其监测与研究,及时报告中药注射液不良反应,有助于减少和避免中药注射液不良反应的发生,保障患者用药安全。     

浅析中药注射剂的风险与对策

目的：分析中药注射剂致不良反应发生的原因和应对措施,以促进临床合理用药。方法：根据相关文献对中药注射剂不良反应发生的原因和应对措施进行总结。结果：中药注射剂的风险因素包括药物因素、药物相互作用、原料选取生产工艺、个体差异、给药方法等。结论：在生产上要加强管理;加强安全性研究与监测,建立监管档案;提高医生素质及时监测中药注射剂不良反应,多管齐下以保证中药注射剂的安全使用。     

尿苷二磷酸葡萄糖醛酸转移酶的调控及其介导的中药-药物相互作用研究进展

尿苷二磷酸葡萄糖醛酸转移酶（UGT）催化的葡萄糖醛酸化反应是的是Ⅱ相代谢中重要的代谢反应之一,对于维持内源性化合物如胆红素、胆汁酸的动态平衡和药物、致癌物等外源性化合物的处置过程起着至关重要的作用。UGTs的表达和酶活性受多维机制的调控。深入研究其调控网络以及UGT介导的相关中药-药物相互作用,对于临床更安全、有效的使用中药提供了指导。因此,本文总结了尿苷二磷酸葡萄糖醛酸转移酶的转录前、转录水平、翻译后修饰等分子调节机制,以及由UGT介导的中药-药物相互作用相关的研究进展。     

体外代谢体系中中药及其成分对肝脏CYP450代谢酶抑制作用的研究进展

细胞色素P450 (CYP450)是肝微粒体中参与体内I相代谢反应的酶,临床上90%以上的药物都经CYP450氧化代谢,其被诱导或抑制是引起药物相互作用的主要机制。通过离体器官、细胞或酶系统进行的体外代谢研究以其精准、简化等特点近年来发展迅速。中药的体外代谢研究可推断药物可能的代谢途径和参与代谢的CYP450酶,研究药物的相互作用,更好地解释中药及其成分的作用机制,促进临床合理用药。本文就中药、中药成分、中药提取物在不同种属肝微粒体中对CYP450代谢酶活性的抑制作用进行综述,以期为中药-中药、中药-化学药物之间相互作用研究提供借鉴与参考。     

临床安全用药应重视药物相互作 用简

目的 探讨药物相互作用与安全用药的关系.方法 从药物相互作用的分类及如何减少不利相互作用等方面,探讨临床安全用药.结果 可从实施个体化给药、重视药品说明书、重视发生药物相互作用的高风险人群用药及易发生药物相互作用的高风险药物等方面减少不利药物相互作用.结论 重视药物相互作用,对提高医疗质量和安全有效地联合用药极为重要.     

Herbal drugs for diabetic treatment: an updated review of patents

Diabetes mellitus is the most common endocrine disorder, affecting 16 million individuals in the United States and 200 million worldwide. Despite the use of advanced synthetic drugs for the treatment, use of herbal remedies is gaining higher importance because of synthetic drugs have drawbacks and limitations. The herbal drugs with antidiabetic activity are extensively formulated commercially because of easy availability, affordability and less side effects as compared to the synthetic antidiabetic drugs. Antidiabetic herbal formulations (AHF) are considered to be more effective for the management of diabetes. There are around 600 herbal drug manufacturers in India of which almost all manufacturers are developing AHF in addition to others. Till date, no article is published to give detailed information of the patents on AHF. Thus, this review article undertake the attempt for providing updated information on the type of diabetes and patented AHF which will enhance the existing knowledge of the researchers.     

Pharmacokinetic herb-drug interactions: are preventive screenings necessary and appropriate?

Pharmacokinetic interactions often occur as a result of activity changes of drug-metabolizing and transporting proteins, especially cytochrome P450 (CYP) isoenzymes and P-glycoprotein (P-gp). The activity of these enzymes and drug transporters can be enhanced or inhibited by synthetic drugs as well as by natural products. Since the number of herb-drug interactions has increased in recent years, systematic in vitro screenings and more clinical studies to identify such interactions were proposed for herbal medicinal products. However, previous results regarding this issue are not only contradictory but also of less predictability. One reason for the discrepancies could be the lack of validation of the recommended in vitro tests. Furthermore, it has to be considered that pharmacokinetic drug interactions are not only mediated by herbal medicines but also by several foods, beverages and life-style products. Since herbal medicines are considered to have a broad therapeutic range, a preventive risk assessment for pharmacokinetic drug interactions should first be realized for synthetic drugs with a narrow therapeutic index. Efforts to identify all possible interactions will lead to limitless investigations and to inconsistent decisions.     

Drug interactions in African herbal remedies

Herbal usage remains popular as an alternative or complementary form of treatment, especially in Africa. However, the misconception that herbal remedies are safe due to their "natural" origins jeopardizes human safety, as many different interactions can occur with concomitant use with other pharmaceuticals on top of potential inherent toxicity. Cytochrome P450 enzymes are highly polymorphic, and pose a problem for pharmaceutical drug tailoring to meet an individual's specific metabolic activity. The influence of herbal remedies further complicates this. The plants included in this review have been mainly researched for determining their effect on cytochrome P450 enzymes and P-glycoprotein drug transporters. Usage of herbal remedies, such as Hypoxis hemerocallidea, Sutherlandia frutescens and Harpagophytum procumbensis popular in Africa. The literature suggests that there is a potential for drug-herb interactions, which could occur through alterations in metabolism and transportation of drugs. Research has primarily been conducted in vitro, whereas in vivo data are lacking. Research concerning the effect of African herbals on drug metabolism should also be approached, as specific plants are especially popular in conjunction with certain treatments. Although these interactions can be beneficial, the harm they pose is just as great.     

271例门诊病人中药咨询情况调查与分析

目的 :通过对271例门诊病人中药咨询情况的调查与分析 ,明确开展中药咨询工作的必要性和实用性。方法 :我院1999年4月至2000年1月 ,解答有关病人提出的中药方面的问题1334人次 ,随机抽取271例门诊病人咨询情况进行综合分析。结果 :病人要求推荐用药的最多 ,占29 2 % ;咨询药物相互作用、用法用量、中成药适应证、不良反应、中药汤药的煎服方法、药品价格的分别占14 0 %、12 9 %、11 1 %、5 5 %、5 2 %和5 2 % ;通过咨询发现了临床不合理用药情况及咨询中存在的问题。结论 :药物咨询对指导病人安全、有效、经济地用药具有重要价值     

Importance of metabolic activation study to the safe use of Chinese herbal medicines

The number of new drugs approved for clinical use per year is falling in the last decade. One approach to reduce the high rate of attrition during early drug development is to systematically determine the toxic metabolites on the mechanism basis. Traditional Chinese herbal medicines (CHM) have been used extensively for disease treatment and health care. Recently, they have also been used as raw materials for preparation of herbal dietary supplements and nutraceuticals worldwide. However, problems arise due to the adverse effects caused by CHM and their derived products. Similar to synthetic drugs, among the diverse mechanisms the metabolism-induced adverse effect/toxicity is an important safety issue of CHM. For safe use of CHM and herbal products, it is also necessary to study herbinduced toxicities using the mechanism-based approach. CHM consist of multi-ingredients, which makes the study of toxic metabolites more difficult and challenging than that of synthetic drug-induced toxicity. In this mini-review, using hepatotoxicity and nephrotoxicity induced respectively by metabolic activation of pyrrolizidine alkaloids and aristolochic acid present in CHM as examples, we address the significance of metabolic study of CHM and how it contributes to the delineation of the toxic mechanisms, development of mechanismbased biomarkers for the diagnosis and assessment of adverse effect/toxicity of CHM, prediction of toxic dosage, and reduction and prevention of toxicity of CHM.     

Evaluation of metabolism-mediated herb-drug interactions

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.     

Biopharmaceutical characterisation of herbal medicinal products: are in vivo studies necessary?

Herbal medicinal products have to meet comparable standards concerning the assessment of efficacy, safety and (bio)pharmaceutical quality as chemically defined synthetic drugs. However, these requirements are not fulfilled for many herbal products so far, particularly regarding in vitro dissolution and in vivo bioavailability. The necessity of in vivo studies for a biopharmaceutical characterisation of the products depends on the solubility/permeability properties of the active drug ingredient as well as dissolution behaviour of the dosage form. Also, in the case of herbal medicinal products, a waiver of in vivo BA/BE studies is recommended as long as the active ingredient is highly soluble according to the Biopharmaceutics Classification System and dissolution of the dosage form takes place rapidly (>85%/20 min) in physiological buffer systems (pH 1-8).     

Detection of undeclared erectile dysfunction drugs and analogues in dietary supplements by ion mobility spectrometry

An ion mobility spectrometry (IMS) method was developed to screen for the presence of undeclared synthetic erectile dysfunction (ED) drugs or drug analogues in herbal dietary supplements claiming to enhance male sexual performance. Ion mobility spectra of authenticated reference materials including three FDA approved drugs (sildenafil citrate, tadalafil, vardenafil hydrochloride trihydrate) and five previously identified synthetic analogues (methisosildenafil, homosildenafil, piperidenafil, thiosildenafil, thiomethisosildenafil) were measured to determine their reduced ion mobilities (K₀). All eight compounds exhibited reduced mobilities between 0.8257 and 1.2876 cm²/(V s). Twenty-six herbal products were then screened for the presence of these compounds, and 15 of the 26 products tested positive for the presence of ED drug or drug analogue adulterants based on their reduced ion mobilities. IMS results were compared against the results obtained from an independent LC/MS reference method for the identical samples. Herbal dietary supplements containing adulterants were classified with 100% accuracy and most of the adulterants were correctly identified by a comparison of the K₀ of the adulterant to the K₀ of the authenticated reference material. The results demonstrate that IMS is a viable method for screening herbal dietary supplements for the presence of ED drug or drug analogue adulterants.