伊马替尼药动学相关的药物相互作用研究进展

伊马替尼是治疗慢性粒细胞白血病的一线药物，它在体内经多种CYP450代谢酶和转运体作用，临床多种合用药物可能通过不同的相互作用机制改变其在体内的过程，甚至引起显著的临床意义。本文综述并探讨了不同种类药物对伊马替尼药代动力学的影响，促进伊马替尼的临床安全、有效用药。     

中枢神经抑制药与其它药物的相互作用

中枢神经抑制药与其它药物的相互作用高宏科（河北省峰峰矿务局第二医院邯郸０５６２０１）中枢神经抑制药是一类应用较广的药物，常难免与其它药物同服，本文旨在探讨该类药物与它药合用时的相互作用问题，以供临床用药时参考。１．苯妥英与丙戊酸ＭＬＬａｉ等对１２例男...     

常用抗精神病药及其与相关药物的相互作用

调查显示，目前临床使用频率较高的抗精神病药依次是氯氮平、利培酮、舒必利、氯丙嗪，治疗过程中由于药源性及并发症等各种原因常合并使用其他药物，最常合并使用的药物是抗胆碱能药、苯二氮革类药、β-受体阻断药、抗抑郁药和心境稳定药。鉴于抗精神病药与肝脏细胞色素P450（CYP450）酶系关系密切，容易与多种药物产生具有临床意义的药物相互作用，导致药理作用和毒副作用的改变，故了解本类药物相关的药物相互作用对指导临床合理用药具有重要意义。     

利伐沙班与临床常用药的药物相互作用研究进展

利伐沙班作为一种特异性凝血因子Xa抑制剂在临床上被广泛应用于抗凝的预防及治疗中。然而,在临床应用过程中,利伐沙班与其他药物合用所致的出血风险仍需密切监视。聚焦药物代谢酶及转运体,分别从利伐沙班与心血管系统药物、抗肿瘤药物、以及代谢靶点相关药物合用等方面系统综述药动学介导的利伐沙班相关药物-药物相互作用的研究进展,旨在为利伐沙班的临床安全合理用药提供更科学、更直接的指导依据。     

基于细胞色素P450酶的药物相互作用机制探讨

细胞色素P450酶是药物体内代谢的关键酶,药物合用时可能因与同一种代谢酶的相互作用,导致药物在体内的处置过程发生改变.本文旨在探讨常见的细胞色素P450酶相关药物相互作用类型和其机制,为临床联合用药的合理、安全、有效提供依据.     

药代动力学人体预测及其在新药研发中的应用

药物代谢和药代动力学(DMPK)通过揭示药物的体内代谢处置过程,理解药物药理效应和毒副反应的体内物质基础,是连接药物分子及其性质与生物学效应的桥梁。DMPK人体预测应用模型拟合技术,由人体外试验数据和动物体内外数据预测人体药代动力学性质,并与药效动力学和毒性评价相关联,可提高新药研发效率、降低临床失败率和节省资源。经典的异速放大法和体外-体内外推法主要用于预测人体清除率和稳态表观分布容积等重要的药代动力学参数。近10年来,基于生理的药代动力学模型(PBPK)的快速发展和应用实践,推动了DMPK人体预测在新药研发、药物监管、临床合理和个体化用药中的应用。PBPK模型不仅能预测消除和分布等参数,还能用于药物人体药代动力学行为的预测,包括血药浓度-时间曲线和药物-药物相互作用,以及不同人群体内药代动力学和药代-药效预测。作为新药研发的转化科学技术以及个体化用药的指导工具,DMPK人体预测将具有更为广泛的应用价值。     

小柴胡汤与化学药联合应用及两者相互作用的研究概况

目的:了解小柴胡汤与化学药联合应用及两者相互作用的研究现况,为其临床用药及深入研究提供参考。方法:以"小柴胡汤""化学药""药-药相互作用""药物代谢酶""细胞色素""药动学""药效学""Xiaochaihu decoction""Xiaochaihu Tang""Sho-saiko-to""Chemical drugs""Herb-drug interactions""Drug-metabolizing enzymes""Cytochrome""Pharmacokinetics""Pharmacodynamics"等为关键词,在中国知网、万方数据、维普网、PubMed等数据库中组合查询1998年1月-2018年7月发表的相关文献,对小柴胡汤联合化学药治疗消化系统疾病、心脑血管系统疾病、免疫相关疾病以及其他疾病的用药情况及其对联用化学药吸收及代谢的影响进行论述。结果:共检索到相关文献7 337篇,其中有效文献49篇。其中,关于小柴胡汤与化学药联合用药的临床疗效观察较多,且小柴胡汤分别与雷贝拉唑、单硝酸异山梨酯、恩替卡韦等化学药联用在消化、心脑血管、免疫等系统疾病中均可取得较好的临床效果。而有关两者相互作用机制的研究则较为有限,只有少量文献报道小柴胡汤可通过影响联用化学药的吸收与代谢等体内过程而发生药物相互作用。结论:临床上小柴胡汤与化学药联用广泛,大多联用的治疗效果优于化学药的单用,两药联用存在潜在的药物相互作用而影响药效,今后可以从小柴胡汤对肝药酶的影响等方面入手加强相互作用机制研究。     

影响药物代谢的因素与临床用药

了解影响药物在体内代谢的因素,监护病人的药物治疗,提供最佳治疗方案,使临床用药合理化。本文就药物与机体之间的相互关系,药物在体内的相互作用,影响药酶活性而改变药物的血浓度,疾病和其它因素对药物代谢的影响以及临床用药如何提高疗效,降低药物的毒副反应,作一概述。     

姜黄素对药物转运体影响的研究进展

目的:就姜黄素对药物转运体的影响进行综述,为临床合理用药提供参考。方法:对近年来相关研究及国内、外的相关文献进行总结归纳。结果:姜黄素可以调节P-糖蛋白活性或表达,若合用可影响P-糖蛋白底物的药动学,增加耐药细胞对化疗药物的敏感性;姜黄素也可调节乳腺癌多药耐药蛋白、多药耐药相关蛋白的活性或表达。结论:姜黄素与其他药物合用需注意其可能引起的药物相互作用,且姜黄素有望成为化疗增敏剂。     

心血管临床药师提高患者用药依从性案例分析

<正>患者用药依从性差,会对疾病治疗产生重大影响,甚至危及生命。我国医学、药学教育的差异性造成医师在病例诊断方面有优势,而临床药师对药物在体内的药代动力学、药物与机体的相互作用、时辰药理、药剂学等比较了解[1]。临床药师参与临床药物治疗,参与个体化给药方案的设计,并对患者进行用药指导,对提高患者用药依从性具有重要意     

中山市住院流浪精神病患者用药现况调查

目的：了解中山市住院流浪精神病患者的用药情况。方法采用横断面调查方法,以2O13- O7-17为时间点,对中山市第三人民医院住院流浪精神病患者的用药情况进行调查。结果使用频率最高的抗精神病药物是利培酮,其次是氯氮平和奋乃静;使用一种抗精神病药物患者83例,两种抗精神病药物联用患者9例;使用心境稳定剂患者32例,抗精神病药物与心境稳定剂联用者26例;使用抗抑郁药患者1例;使用苯二氮卓艹类药物患者23例。结论中山市住院流浪精神病患者使用的抗精神病药物以第二代抗精神病药物为主,注重心境稳定剂、抗抑郁药及苯二氮卓艹类药物的使用,兼顾关注患者的躯体情况,从医疗用药方面体现了中山市对流浪精神病患者救治的重视。     

心境稳定剂在精神疾病治疗中的应用

目前临床上常用的心境稳定剂包括锂盐、抗惊厥药物和非典型抗精神病药物。此外,现还新上市了一些具有潜在心境稳定作用的药物或辅助用药。本文概要介绍主要心境稳定剂及其在精神疾病治疗中的应用。     

Antidepressant properties of anticonvulsant drugs for bipolar disorder

A growing number of anticonvulsant drugs are receiving attention as possible mood stabilizers. This attention is based mainly on the assumption that the antimanic efficacy of anticonvulsants makes them suitable as mood stabilizers. However, their antidepressant properties have received less scrutiny. In this review, current evidence concerning the acute and prophylactic efficacy of divalproex, carbamazepine, gabapentin, lamotrigine, and topiramate in bipolar depression is evaluated. Clinical outcome data are considered, together with limitations of existing studies and the concept of unmet clinical needs. Findings in placebo-controlled trials suggest an acute and prophylactic antidepressant effect with lamotrigine monotherapy and more modest antidepressant benefits with other agents administered as monotherapies. Results of published studies are considered with respect to the conceptualization of mood stabilization as arising from antimanic and antidepressant efficacy in bipolar disorder.     

河北省双相障碍患者药物治疗现状的调查分析

目的:为促进河北省双相障碍患者治疗的规范化、合理化,特别是为提高基层的临床治疗水平提供参考。方法:选取在河北省39家精神专科医院或综合医院精神科接受精神药物治疗的门诊或住院双相障碍患者,通过问卷调查患者的药物治疗情况,并对数据进行统计分析。结果:共发放问卷521份,回收有效问卷519份,有效回收率为99.6%。397例(76.5%)患者接受心境稳定剂治疗,使用频率排前3位的分别为丙戊酸钠、碳酸锂和丙戊酸镁;455例(87.7%)患者接受抗精神病药治疗,使用频率排前5位的分别为喹硫平、奥氮平、利培酮、氯氮平和阿立哌唑;89例(17.1%)患者接受抗抑郁药治疗,其中73.0%使用选择性5-羟色胺再摄取抑制剂;154例(29.7%)患者接受苯二氮类药物治疗,47例(9.1%)患者辅以抗胆碱药物治疗,27例(5.2%)患者辅以β受体阻滞药治疗。双相障碍治疗以联合用药为主,428例(82.5%)患者联合2种以上精神药物治疗,以心境稳定剂联合抗精神病药为主;且抗抑郁药使用以联合心境稳定剂或抗精神病药为主。住院患者心境稳定剂的使用与门诊患者比较,差异有统计学意义(P<0.01),丙戊酸钠的使用频率低于门诊患者,碳酸锂和丙戊酸镁的使用频率高于门诊患者;住院患者接受抗抑郁药治疗的比例显著低于门诊患者,二者比较差异有统计学意义(P<0.05)。结论:河北省双相障碍患者的治疗以心境稳定剂联合抗精神病药为主要的方式;抗精神病药的使用比例较高,以非典型抗精神病药为主;抗抑郁药的使用以联合用药为主;心境稳定剂在住院与门诊的选择有所不同,且抗抑郁药门诊使用比例较高。双相障碍患者的治疗总体符合双相障碍防治指南的推荐用药原则。     

Pharmacotherapy of borderline personality disorder: a systematic review for publication purpose

Borderline Personality Disorder (BPD) is a common disorder in psychiatric practice and drugs are widely used in its treatment, targeting symptom clusters, such as affective dysregulation, impulsive-behavioural dyscontrol, and cognitive-perceptual symptoms. In last period, a growing number of studies on pharmacological treatment of BPD have been performed, but different proposals of treatment guidelines are not completely in accordance on drug indications for BPD patients. This article reviews double-blind randomized controlled trials comparing active drugs versus placebo and drugs versus drugs, published between 1990 and 2010 and focused on the treatment of borderline personality disorder. Different classes of psychoactive agents, such as antipsychotics, mood stabilizers, antidepressants, and dietary supplementation were tested in BPD patients. More recent evidences suggest that mood stabilizers (topiramate, valproate and lamotrigine), second generation antipsychotics (olanzapine and aripiprazole) and omega-3 fatty acids can be useful to treat affective symptoms and impulsive-behavioural dyscontrol in BPD patients. Moreover, antipsychotics significantly improve cognitive symptoms in patients with BPD. SSRIs were found effective in decreasing severity of depressed mood, anxiety and anger, mainly in subjects with a concomitant affective disorder. Effects of antidepressants on impulsive behaviours are uncertain. Further studies are needed to improve methods of trials and confirm these findings.     

Associations between proteins and heavy metals in urine at low environmental exposures: evidence of reverse causality

Mitochondria represent a possible drug target with unexplored therapeutic and toxicological potential. The possibility was suggested that antidepressants, mood stabilizers and other drugs may show some therapeutic and/or toxic effects through their action on mitochondrial functions. There are no sufficient data about the effect of these drugs on mitochondrial respiration in the brain. We investigated the in vitro effects of amitriptyline, fluoxetine, tianeptine, ketamine, lithium, valproate, olanzapine, chlorpromazine and propranolol on mitochondrial respiration in crude mitochondrial fractions of pig brains. Respiration was energized using substrates of complex I or complex II and dose dependent drug-induced changes in mitochondrial respiratory rate were measured by high-resolution respirometry. Antidepressants, but not mood stabilizers, ketamine and propranolol were found to inhibit mitochondrial respiratory rate. The effective dose of antidepressants reaching half the maximal respiratory rate was in the range of 0.07-0.46mmol/L. Partial inhibition was found for all inhibitors. Differences between individual drugs with similar physicochemical properties indicate selectivity of drug-induced changes in mitochondrial respiratory rate. Our findings suggest that mood stabilizers do not interfere with brain mitochondrial respiration, whereas direct mitochondrial targeting is involved in mechanisms of action of pharmacologically different antidepressants.     

A review of the evidence for carbamazepine and oxcarbazepine in the treatment of bipolar disorder

Bipolar disorder is a recurrent lifelong condition associated with significant morbidity and mortality. The main goals of treatment are the acute management of manic/depressive episodes and the prevention of recurrence. Mood stabilizers are the basis of most treatment regimens. Although lithium is the classical mood stabilizer, dissatisfaction with its efficacy and tolerability has led to increased use of other mood- stabilizing agents, including anticonvulsants. Newer anticonvulsants such as oxcarbazepine may offer improved tolerability and fewer drug-drug interactions compared to older drugs like carbamazepine. A search of the literature shows that data from controlled clinical studies support the efficacy of carbamazepine in treating acute mania and as maintenance therapy. In addition, a growing body of data for oxcarbazepine suggests that this newer agent may have a similar efficacy profile to carbamazepine, with improved tolerability. This review presents a balanced selection of the key studies on carbamazepine and oxcarbazepine in bipolar disorder.     

The supra-additive hyperactivity caused by an amphetamine-chlordiazepoxide mixture exhibits an inverted-U dose response: Negative implications for the use of a model in screening for mood stabilizers

One of the few preclinical models used to identify mood stabilizers is an assay in which amphetamine-induced hyperactivity (AMPH) is potentiated by the benzodiazepine chlordiazepoxide (CDP), an effect purportedly blocked by mood stabilizers. Our data here challenge this standard interpretation of the AMPH-CDP model. We show that the potentiating effects of AMPH-CDP are not explained by a pharmacokinetic interaction as both drugs have similar brain and plasma exposures whether administered alone or in combination. Of concern, however, we find that combining CDP (1-12 mg/kg) with AMPH (3 mg/kg) results in an inverted-U dose response in outbred CD-1 as well as inbred C57Bl/6N and 129S6 mice (peak hyperactivity at 3 mg/kg CDP + 3 mg/kg AMPH). Such an inverted-U dose response complicates interpreting whether a reduction in hyperactivity produced by a mood stabilizer reflects a “blockade” or a “potentiation” of the mixture. In fact, we show that the prototypical mood stabilizer valproic acid augments the effects of CDP on hypolocomotion and anxiolytic-like behavior (increases punished crossings by Swiss-Webster mice in the four-plate test). We argue that these data, in addition to other practical and theoretical concerns surrounding the model, limit the utility of the AMPH-CDP mixture model in drug discovery.     

Evaluation of the effects of propylisopropylacetic acid (PIA) on neuronal growth cone morphology

Propylisopropylacetic acid (PIA) is a constitutional isomer of valproic acid (VPA). It has previously been found to be a weak antiepileptic, but in common with mood stabilizers, causes inositol depletion and growth cone spreading, suggesting the basis of a new series of mood stabilizers. To assess this possibility, we have compared the effects of racemic (R,S)-PIA and its individual enantiomers to those of the mood stabilizers lithium (Li⁺), VPA and carbamazepine (CBZ). Unlike Li⁺ and VPA, but in common with CBZ and (R,S)-PIA, neither (R)-PIA nor (S)-PIA enantiomer induces T-cell factor (TCF)-mediated gene expression. However, as seen for other mood stabilizers, both enantiomers are potent inducers of growth cone spreading. To investigate the mechanism for these effects, we examined changes in the actin cytoskeleton following drug treatment with Li⁺, VPA, CBZ, (R,S)-PIA or its individual enantiomers. All exhibit a re-distribution of F-actin to the growth cone periphery, a feature of spread growth cones. (R,S)-PIA has the strongest effect as it also elevates F-actin polymerization at the cell periphery. This change in the actin cytoskeleton is associated with a substantial increase in F-actin-rich protrusions on the surface of the growth cone and in its close vicinity. These results demonstrate an effect of (R,S)-PIA on the neuronal actin cytoskeleton shared in common with other mood stabilizers, and suggest a potential to induce structural changes within the CNS.