格列奈类药物的药动学及与其他药物的相互作用

格列奈类药物吸收迅速,t_(1/2)短,单一疗法耐受性良好,不良反应发生率低于磺脲类药物,但与其他药物联用时,可能发生与CYP3A4、CYP2C8及CYP2C9同工酶和有机阴离子转运多肽1B1(OATP1B1)转运体相关的药动学相互作用,从而降低药物疗效或增加低血糖等不良事件的风险。本文就格列奈类药物的药动学性质及与其他药物的药动学相互作用作一综述。     

葡萄柚汁与药物的相互作用

目的：了解葡萄柚汁对其他药物代谢的影响及合用后的相互作用。方法：通过对近几年来的国内外文献报道进行收集，归纳，分析，加以综述。结果：葡萄柚汁可改变许多药物的药动学，使血药浓度升高，引起有临床意义的食物－药物相互作用。结论：临床上应尽量避免葡萄柚汁与易受影响的药物，如二氢吡啶类钙拮抗剂，免疫抑制剂，许多中枢神经系统药物，他汀类药物，促胃肠动力药沙必利，HIV蛋白酶抑制剂等合用，以确保用药安全。     

他汀类药物与其他药物的相互作用

目的：部分脂溶性他汀药物是CYP3A4／5的底物，其代谢易被其他药物所诱导或抑制，也可能抑制其他药物的代谢，本资料拟总结上述常见的相互作用，供临床用药参考。方法：检索Medline1966—2006年期间公开发表的他汀类与其他药物代谢方面的相互作用文献，进行分析、归纳。结果：他汀类药物与临床经常合用的其他药物包括口服抗凝药、抗感染药物、其他调血脂药物、抗HIB药物等存在临床意义的相互作用。结论：临床对于他汀类药物与其他药物联合应用时应该谨慎，注意避免或减少不良相互作用，保障用药安全有效。     

PBPK模型在抗菌药物与其他药物相互作用中的应用

细菌感染是临床上常见的并发症，而抗菌药物作为广泛应用的抗感染类药物，常与免疫抑制剂、抗肿瘤类药物等联合使用。由于存在潜在的药物-药物相互作用(DDIs)，抗菌药物与其他药物的共同给药仍然具有挑战性。近年来，基于生理的药动学(PBPK)模型越来越多地用于预测药物-药物相互作用，从而更好的指导治疗方案和药物剂量的选择。本文将对PBPK模型的概念及其在抗菌药物与其他药物相互作用方面的应用作一综述，以期为临床抗菌药物的合理使用提供理论和循证依据。     

国产与进口他汀类药说明书在药物相互作用方面的差异

目的:对比国产与进口他汀类药说明书提供的药物相互作用关键性信息。方法:收集相关他汀类药(辛伐他汀、阿托伐他汀、氟伐他汀和瑞舒伐他汀)说明书,仔细阅读并进行比较。结果与结论:所有药动学相互作用包括可能产生效应的相关数据及相互作用机制都需体现在药品说明书中,以便确保其合理、安全使用。多数国产他汀类药说明书提供的相互作用信息均比较全面,与进口药说明书表述的信息相接近;只有少数国产药说明书所列举的他汀类药相互作用信息过于简单。相比之下,进口他汀类药说明书含有更多的相关信息及数据。建议药品生产企业在说明书中增加更多的药物相互作用机制及数据信息介绍,以便为临床用药提供更多的帮助。     

瑞舒伐他汀药代动力学及与其他药物的相互作用研究进展

瑞舒伐他汀是新一代他汀类药物,相对之前的他汀类药物,肝选择性更好;肝代谢少、消除半衰期长,具有更强的降脂作用,临床应用前景广泛;其耐受性良好,不良反应发生率与同类其他药物相似。本文对瑞舒伐他汀的药代动力学及与其他药物相互作用作一综述。以期为指导瑞舒伐他汀的临床用药打下坚实的理论基础,确保临床用药的安全性和有效性,真正实现临床上的个体化给药。     

环孢素与降血脂药物在器官移植患者中的相互作用

目的:综述环孢素与降血脂药物在器官移植患者中的相互作用.方法:查阅相关文献,加以综述.结果:他汀类药物的药动学可受环孢素的影响;纤维酸衍生物和环孢素是否存在相互作用尚还没有明确的结论;环孢素与胆汁酸螯合剂没有直接的显著相互作用;鱼油、普罗布考和奥利斯特均可影响环孢素的药动学.结论:环孢素和降脂药物之间相互作用研究有着重要的意义.     

氨氯地平与其他药物的相互作用研究进展

氨氯地平属于第三代钙离子拮抗剂（CCB）,主要用于心脑血管疾病的治疗。近期的研究发现,氨氯地平与多种药物存在相互作用,这些相互作用主要体现在药动学和药效学两个方面。药动学相互作用主要与肝药酶CYP450以及转运体P-gP（P-糖蛋白）有关。氨氯地平是CYP450和P-gp的底物,影响肝药酶或P-gp活性的药物,如抗病毒药物利托那韦、抗真菌药物伊曲康唑以及大环内酯内抗生素他克莫司等均可改变氨氯地平的药动学特征。药效学相互作用主要表现办疗效的改变,他汀类药物、血管紧张素转化酶抑制剂（ACEI）药物以及血管紧张素Ⅱ受体拮抗剂（ARB）等与氨氯地平具有协同作用,而氯吡格雷等其他药物与氨氯地平合用时,氨氯地平的疗效降低甚至失效。本文就近年来关于氨氯地平的相互作用研究做一综述。     

3种他汀类药物联合用药处方分析

目的了解他汀类药物的合并用药情况,为临床合理用药提供参考。方法在代谢酶学理论指导下,从代谢性相互作用的角度对处方进行回顾性分析。结果含3种他汀类药物的处方共计2 267张,其中含氟伐他汀和CYP2C9抑制药或底物的处方208张;含阿托伐他汀或辛伐他汀,且有CYP3A4抑制药或底物的处方分别为412和56张。厄贝沙坦、氨氯地平、硝苯地平、那格列奈、泼尼松、非洛地平等出现的频率较高。结论他汀类药物应避免与抑制他汀类药物代谢的药物合用,或选择无或很少相互作用的同类药物。药师在合并用药中应做好处方审查和患者用药教育,必要时对某些可疑相互作用进行血药浓度监测。     

他汀类药物与其他药物的相互作用

3-羟-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂(他汀类)之间存在药动学差异,使它们与其他药物发生相互作用的机制及程度不同。主要经细胞色素P450(CYP)3A4酶代谢的洛伐他汀、辛伐他汀、阿托伐他汀、西立伐他汀的药物相互作用多见,其中,西立伐他汀因其致命性横纹肌溶解已被迫退出世界市场。经CYP2C9酶代谢的氟伐他汀、罗舒伐他汀与其他药物联合应用时,肌病发生率很低。而不通过CYP系统代谢的普伐他汀耐受性好,肌病及肝功能异常者罕见。     

Adverse pharmacokinetic interactions between illicit substances and clinical drugs

Abstract

Adverse pharmacokinetic interactions between illicit substances and clinical drugs are of a significant health concern. Illicit substances are taken by healthy individuals as well as by patients with medical conditions such as mental illnesses, acquired immunodeficiency syndrome, diabetes mellitus and cancer. Many individuals that use illicit substances simultaneously take clinical drugs meant for targeted treatment. This concomitant usage can lead to life-threatening pharmacokinetic interactions between illicit substances and clinical drugs. Optimal levels and activity of drug-metabolizing enzymes and drug-transporters are crucial for metabolism and disposition of illicit substances as well as clinical drugs. However, both illicit substances and clinical drugs can induce changes in the expression and/or activity of drug-metabolizing enzymes and drug-transporters. Consequently, with concomitant usage, illicit substances can adversely influence the therapeutic outcome of coadministered clinical drugs. Likewise, clinical drugs can adversely affect the response of coadministered illicit substances. While the interactions between illicit substances and clinical drugs pose a tremendous health and financial burden, they lack a similar level of attention as drug-drug, food-drug, supplement-drug, herb-drug, disease-drug, or other substance-drug interactions such as alcohol-drug and tobacco-drug interactions. This review highlights the clinical pharmacokinetic interactions between clinical drugs and commonly used illicit substances such as cannabis, cocaine and 3, 4-Methylenedioxymethamphetamine (MDMA). Rigorous efforts are warranted to further understand the underlying mechanisms responsible for these clinical pharmacokinetic interactions. It is also critical to extend the awareness of the life-threatening adverse interactions to both health care professionals and patients.     

CYP450与药物相互作用

目的 探讨细胞色素P450（CYP450）与药物相互作用的关系.方法 检索国内外数据库中与药物相互作用的相关文献,并查阅相关书籍,总结CYP450酶与药物相互作用的关系.结果 CYP450与药物相互作用关系最密切的是酶系统,凡参与代谢的酶都与药物相互作用有关,其中最主要的是CYP1 A2,2C9,2C19,2D6,3A4.结论 充分了解药物的药理及药代动力学特点,当与可能发生相互作用的药物合用时,应密切监测患者的情况,必要时进行药物剂量调整或换用其他药物.     

Statin drug interactions and related adverse reactions

Introduction: Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Because statins are prescribed on a long-term basis, their possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment.

Areas covered: This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions and related adverse reactions.

Expert opinion: Avoiding drug–drug interactions and consequent adverse drug reactions is essential in order to optimize compliance, and thus improve the treatment of patients at high cardiovascular risk. The different pharmacokinetic profiles among statins should be carefully considered, in order to understand the possible spectrum of drug interactions. The growing trend toward earlier statin treatment for the prevention of cardiovascular disease means that physicians must anticipate future polypharmacy when their patients require additional medications for comorbid conditions.     

手性药物对映体在药效学与药代动力学的相互作用

当手性药物以外消旋体供药用时，其对映体间就可能发生药效学和药代动力学的相互作用。本文综述了手性药物对映体间的药效学和药代动力学相互作用及其对手性药物药效学和药代动力学立体选择性的影响。     

Medical Consequences of Drug Abuse and Co-Occurring Infections: Research at the National Institute on Drug Abuse

ABSTRACT

Substance abuse still remains one of the major problems in the world today, with millions of people abusing legal and illegal drugs. In addition, a billion people may also be infected with one or more infections. Both drugs of abuse and infections are associated with enormous burden of social, economic, and health consequences. This article briefly discusses a few medical consequences of drugs of abuse and infections such as human immunodeficiency virus, hepatitis C virus, psychiatric complications in hepatitis C infection, pharmacokinetic drug–drug interactions among medications used in the treatment of addiction and infections, and new drugs in development for the treatment of infections. Research is encouraged to study interactions between infections, drugs of abuse, and underlying pathophysiologic and molecular/genetic mechanisms of these interactions.     

转运体在药物排泄中的作用及在新药研发中的意义

本文介绍了药物转运体在药物排泄过程中的作用,探讨了其在新药研发和临床应用中的可能性。通过对药物转运体功能的了解和利用,可以开发出对某些器官有靶向性的药物,或避免药物分布到某些器官中,从而提高药物的疗效,降低其毒副作用;也可以通过对转运体介导的药物相互作用及肝肠循环的研究,指导临床更加安全有效的用药。在药物研发的初始阶段,就开始重视其药动学特性,这一观念近年来已被很多人所接受。对药物转运体的深入认识和利用,建立高通量的药物转运体筛选体系,对于加速新药研发的进程将具有极其重要的意义。     

QT-interval prolongation by non-cardiac drugs: lessons to be learned from recent experience

Background: Evidence has accrued that several non-cardiac drugs may prolong cardiac repolarisation (hence, the QT interval of the surface electrocardiogram) to such a degree that potentially life-threatening ventricular arrhythmias (e.g. torsades de pointes) may occur, especially in case of overdosage or pharmacokinetic interactions. Discussion: This has fostered discussion on the molecular mechanisms underlying the class-III anti-arrhythmic effect shared by apparently disparate classes of drugs, on the clinical relevance of this side effect and on possible guidelines to be followed by drug companies, ethics committees and regulatory agencies in the risk–benefit assessment of new and licensed drugs. This review provides an update on the different classes of non-cardiac drugs reported to prolong the QT interval (e.g. histamine H₁-receptor antagonists, antipsychotics, antidepressants and macrolides), on the possible underlying molecular mechanisms and on the clinical relevance of the QT prolonging effect. Identification and widespread knowledge of risk factors that may precipitate prolongation of the QT interval into life-threatening arrhythmias becomes an important issue. Risk factors include congenital long QT syndrome, clinically significant bradycardia or heart disease, electrolyte imbalance (especially hypokalaemia, hypomagnesaemia), impaired hepatic/renal function and concomitant treatment with other drugs with known potential for pharmacokinetic/pharmacodynamic interactions (e.g. azole antifungals, macrolide antibacterials and class-I or -III anti-arrhythmic agents). Future perspectives for drug research and development are also briefly outlined. Received: 4 October 1999 / Accepted in revised form: 13 January 2000     

Drug–drug interaction with statins

3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors (the so-called statins: atorvastatin, fluvastatin, pravastatin, lovastatin, rosuvastatin and simvastatin) are a well-established class of drugs in the treatment of hypercholesterolemia. Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Since statins are prescribed on a long-term basis, possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment. Moreover, a combination of therapy between statins and other classes of lipid-lowering agents (e.g., ezetimibe, fibrates, resins and nicotinic acid) is recommended for some patients by current guidelines. Therefore, the potential for drug–drug interactions emerges as a relevant factor in determining the safety profile of statins. This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions.     

西沙必利与其他药物的相互作用

目的 了解促胃肠动力药西沙必利与其他药物合用时的相互作用。方法 通过对近期文献的阅读、分析和归纳，加以综述。结果 西沙必利由细胞色素P—450(CYP)3A4代谢，有较强的首过效应，所以许多CYP3A4底物或(和)抑制剂都能抑制西沙必利的代谢，使其血药浓度升高，从而可能引起心脏QT间期延长、心律失常，甚至导致扭转型室速(TdP)。药效学研究表明，西沙必利与可以引起QT间期延长的药物合用后，也可能增加心脏的毒性反应。结论 西沙必利应避免与CYP3A4抑制刑、CYP3A4底物及易引起QT间期延长的药物合用。如果必需合用，应密切观察合用后的情况，并进行心电监护或血药浓度的监测，以保证临床用药的安全有效。