药物胃肠道吸收屏障及新型促吸收方法

胃肠道屏障是机体的重要保护系统,可阻止毒物及抗原的吸收,但也是限制药物吸收的主要因素,导致许多药物的口服生物利用度低,同时也是造成许多具有较好生物活性的候选化合物不能进入后续开发研究的根本原因。许多中药有效成分如人参皂苷类,虽然被普遍认为是人参及其方剂发挥药效作用的主要物质基础,但同时存在口服生物利用度极     

时辰药理学与老年高血压的合理用药分析

药物发挥药效作用的浓度及被人体吸收后的代谢、排泄都呈现一定节律的变化,时辰药理学是研究药物作用与机体昼夜节律相互关系的科学。老年高血压患者由于生理特点比较特殊,故而在选择临床降压药物的过程当中需要引入时辰药理学的相关理念与思路,合理选择药物和用药时间,以减少药物用量,并尽可能发挥药物的最大药效。本文从老年高血压的临床特点阐明时辰药理学与老年高血压的合理用药的关系。     

肠道菌群与药物代谢

肠道菌群具有强大的代谢能力,被认为是人体后天获得的重要"代谢器官",在宿主消化、营养吸收、代谢、免疫等各方面发挥重要作用。肠道菌群参与外源药物等的体内代谢过程及内源糖类、蛋白质、脂肪等的代谢平衡,从而影响药物的体内处置过程、药效-毒性反应以及机体生理、病理状态。     

与功效、毒性相关的何首乌化学成分研究进展

目的总结与功效、毒性相关的何首乌化学成分研究现状,明确何首乌功效成分与毒性成分,为进行何首乌化学成分与功效、毒性相关性研究提供文献依据和研究思路。方法对近十几年来国内外发表的相关文献进行整理、分析、归纳。结果二苯乙烯苷是何首乌的主要化学成分和活性成分,是何首乌发挥功效的主要物质基础;蒽醌类是其可能的毒性成分和毒性表达的主要物质基础。临床报道何首乌可产生多种不良反应,而关于何首乌化学成分毒性的研究报道较少,对于何首乌毒性物质基础、毒性体内过程、毒性作用特点、毒性作用机制研究尚不够深入;目前关于何首乌化学成分、功效和毒性的研究都是孤立的,彼此之间缺少关联性。结论何首乌应在功效和毒性表达导向下进行定向的物质基础分离、合理毒性控制研究,以达到减少不良反应,保证临床安全用药的目的。     

临床药学初步探讨

<正> 临床药剂学是根据药物代谢动力学的理论去研究药物及其剂型的物理、化学性质、给药途径、机体因素、吸收、体内分布、血药浓度、代谢和排泄等有关药物与机体之间复杂的生物转化,以及进入人体后出现的药效与药效强度(生物效应)之间的关系的学科。本文着重就临床药师如何主动配合临     

临床药理学讲座 药效学与临床用药

药理学由药效动力学和药代动力学组成,主要研究药物与机体之间的相互作用。本文重点从药效动力学的角度阐述它与临床用药的关系。1 与药效学有关的基本理论1.1 何谓药效动力学 药效动力学(简称药效学)主要研究药物是如何影响人体的,即药物在人体产生的生理、生化效应及其机制。在理论上,它是药理学的理论基础;在实践上它可指导合理用药,发挥药物的最佳疗效,防止药物的不良反应。1.2 药物作用及作用机理     

对于新药临床前药动学研究的思考和建议

药动学主要研究药物在机体内的吸收(A)、分布(D)、代谢(M)和排泄(E)过程.药动学是新药临床前研究的重要内容,也是临床前药物被淘汰的主要原因.据国外资料报道,在临床前阶段因药动学及相关原因被淘汰的药物占到被淘汰药物总量的18%,药动学成为紧随存安全性之后的导致药物在临床前被淘汰的重要原因.     

不同炮制辅料对何首乌药效成分含量的影响

目的研究不同炮制辅料对何首乌药效成分含量的影响,为选择何首乌炮制辅料提供依据。方法分别采用5种不同炮制辅料制备制何首乌,高效液相色谱法按照2015年版中国药典中制何首乌成分含量测定方法分别测定制何首乌中二苯乙烯苷、游离蒽醌的含量,比较不同炮制辅料对何首乌中药效成分含量的影响。结果炮制辅料基本都会降低制何首乌中二苯乙烯苷和游离蒽醌的含量。不同炮制辅料制备的制何首乌中二苯乙烯苷含量从高到低依次为空白对照何首乌>米泔水制何首乌>生姜汁制何首乌>甘草汁制何首乌>熟地汁制何首乌>黑豆汁制何首乌,游离蒽醌含量从高到低依次为甘草汁制何首乌>空白对照何首乌>米泔水制何首乌>熟地汁制何首乌>黑豆汁制何首乌>生姜汁制何首乌。不同炮制辅料制备的何首乌中二苯乙烯苷含量均高于2015年版中国药典中的要求,而游离蒽醌含量均未达到2015年版中国药典中的要求。结论不同炮制辅料对制何首乌中药效成分含量的影响不同。     

动物生理节律影响药物代谢过程的分子基础及其调节机制的研究进展

实验动物在药物研究与开发领域中发挥着不可替代的作用。药物在体内吸收、分布、代谢及排泄(ADME)过程是其药效或毒性作用产生的前提。国内外研究表明,机体参与药物体内过程各个环节的生理功能状态具有不同程度的时间节律性。肠道转运体、肝脏药物代谢酶及肾脏在药物ADME过程中发挥着重要作用。本文综述了肠道药物转运体、肝脏药物代谢酶及肾脏排泄等环节的生理节律性现象及其分子基础和调节机制。     

浅谈用药与饮食的关系

经多年有关资料研究发现，在服药期间可直接影响药物活性或机体对药物的吸收，增强或降低药效，严重的可导致毒性反应。为了更好地发挥药物的治疗作用，在服药时应做到合理饮食，现总结如下。     

高通量测序和实时荧光定量PCR分析何首乌肝损伤与肠道微生物组的关系

目的采用Illumina高通量测序技术和实时荧光定量PCR（Real-Time PCR,RT-PCR）法研究何首乌（PM）致肝损伤与肠道微生物组间的关系,并验证两种定量方法的一致性。方法雄性SD大鼠随机分为5组：对照组、脂多糖（LPS）组、LPS+对乙酰氨基酚（APAP）组、PM组和LPS+PM组;大鼠尾iv给予4.0 mg/kg LPS建立肝损伤模型,各组相应每天1次ig给予0.625 g/kg APAP和12 g生药/kg PM,记录大鼠体质量;分别于造模后2、14 h、5和8 d,对大鼠粪便中细菌16SrRNA基因的V4高变区进行Illumina高通量测序,根据测序结果得出的差异物种,采用RT-PCR进行验证;取造模后8 d大鼠肝脏组织,HE染色,光学显微镜观察。结果大鼠肝脏病理学检查结果显示,与对照组比较,LPS组大鼠存在肉芽肿,PM组无异常病变;与LPS组比较,LPS+PM大鼠肝细胞出现轻度变性和微小肉芽肿增多,LPS+APAP组可见微小肉芽肿和淋巴细胞浸润。Illumina高通量测序结果提示,与对照组比较,随着PM给药次数增加,单独给予PM的大鼠肠道微生物无显著变化;LPS+PM组表现为肠球菌科和毛螺旋菌科细菌逐渐增加,乳杆菌属细菌减少,且与LPS组有差异;RT-PCR结果显示,与对照组比较,随着PM给药次数的增加,单独给予PM的大鼠肠道微生物无显著变化;LPS+PM组肠球菌科、毛螺旋菌科细菌数显著增加（P<0.05）,乳杆菌属细菌数显著减少（P<0.05）,且与LPS组比较有显著差异。结论 PM肝损伤大鼠存在不同程度的菌群失衡,且Illumina高通量测序和RT-PCR检测结果具有良好的一致性,但Illumina高通量测序技术可获得更多的微生物信息,更具优势。     

中药骨伤凝胶贴剂的经皮渗透性研究

目的 探讨药粉目数及透皮吸收促进剂对中药骨伤凝胶贴剂经皮渗透作用的影响。方法 以羟基红花黄色素A和血竭素为评价指标，采用桨碟法评价凝胶贴剂的体外释放行为，采用Franz扩散池法考察药粉目数及透皮吸收促进剂对凝胶贴剂透皮吸收的影响。结果 与氮酮和薄荷脑相比，肉豆蔻酸异丙酯对于羟基红花黄色素A和血竭素的促渗作用最好，其最佳用量为3%，200目的药粉相对于80目在体外释放及有效成分的经皮吸收方面没有明显影响。结论 药粉目数对凝胶贴剂经皮渗透作用的影响不显著，肉豆蔻酸异丙酯透皮吸收促进剂能显著提高凝胶贴剂的透皮吸收。     

补骨脂及其活性成分在肝损伤中的双重作用研究进展

中药补骨脂是一味传统的补肾壮阳药，但因其滋肾水而涵肝木，有促进肝脏疏泄、调畅气机及抗邪解毒之功效，临床应用广泛。现代药理学研究证实，补骨脂及其部分活性成分是一把“双刃剑”，对肝损伤具有保护作用的同时，也可导致肝损伤。本文就中药补骨脂及其活性成分对肝脏的这种双重作用进行综述，为其进一步开发和利用提供参考。     

泻白散及其主药体外抗氧化活性研究

目的 建立泻白散和方中3味主药甘草、地骨皮、桑白皮的体外抗氧化活性测定方法,并对31批药材和10批泻白散煎液的抗氧化活性进行测定。方法 采用紫外可见分光光度法检测一定浓度的药材提取液引起DPPH溶液吸光度（A）值降低,考察波长为517 nm,分别探索3味药材抗氧化活性成分的提取条件;并进行不同溶剂的吸收考察、专属性考察、DPPH线性考察、药材提取液线性考察、精密度试验、重复性试验、耐用性考察等方法学验证;以清除DPPH自由基的半抑制浓度（IC₅₀）作为评价指标,对泻白散和方中3味药材的体外抗氧化活性进行考察。结果 地骨皮、甘草、桑白皮和泻白散提取液的IC₅₀均值为0.31、1.24、1.49和0.91 g/L,泻白散提取工艺对方中药物抗氧化活性的保留均值为56%。结论 建立的抗氧化活性测定方法可用于泻白散及方中主药的抗氧化活性测定,为多维度评价中药和中药材质量提供新思路。     

Theoretical study of the influence of the circadian rhythm of plasma protein binding on cisplatin area under the curve

A mathematical model for area under the curve (AUC)determination is proposed taking into account the circadian variation of cisplatin protein binding. The main theoretical result obtained with the model is that early morning drug administration (2–4 AM) promotes the highest AUC.The model predicts a maximum AUCvariation, due to the binding variation, ranging between 2.4 and 15%. The minimum of AUCbetween 2.45 and 3.30 PM is in agreement with the minimum nephrotoxicity observed when cisplatin is injected in the afternoon.The model can be applied to other drugs that are irreversively bound to proteins or irreversively bound to other plasma components if the binding rate depends on the time of day. The variation intensity of AUC wasdemonstrated to depend on drug characteristics, but can never be higher than the circadian variation of the protein binding rate.     

中药四环三萜类化合物吸收转运机制研究进展

四环三萜化合物是植物来源中药里具有多种生物活性的一类重要化合物,但研究发现四环三萜类化合物普遍口服生物利用度低,肠吸收不佳,严重影响了该类成分的开发和应用。四环三萜类化合物按照苷元不同大致可以分为达玛烷型、羊毛脂烷型、葫芦素烷型、环阿屯烷型、原帖烷型、楝烷型等几类,总结了不同结构类型的四环三萜化合物单体的肠吸收机制,探讨其肠吸收不佳的原因;综述发现肠吸收多用于研究中药单体、单味中药和中药复方配伍的有效吸收成分及其相互作用规律,并表明中药配伍对有效成分的肠道吸收具有很好的改善作用,以期为改善中药四环三萜类化合物的口服利用度、新剂型的研发设计以及临床的合理用药提供参考。     

A Comparison of Murine and Human Alveolar Macrophage Responses to Urban Particulate Matter

There is increasing evidence linking mortality, increased asthma morbidity, and other respiratory disorders to increases in fine airborne particulate matter (PM) concentrations. However, there are only limited data dealing with the biological mechanisms that ultimately lead to the reported health effects. Rodents are frequently used as an animal model to help elucidate the mechanisms of toxicity that may provide clues for the understanding of PM toxicity in humans; however, the relationships between murine and human PM toxicity have not been established. PM is known to target the pulmonary epithelium and resident alveolar macrophages (AM). PM can initiate cytotoxic effects on the AM including apoptosis and necrosis, depending on the particle concentration, which may be central to the pathological effects just described This study examined AM apoptosis and necrosis initiated by PM in AM from humans and BALB/c mice in an in vitro exposure model. Freshly isolated AM from human volunteers were incubated with seven different residual fractions of PM1648 derived from organic solvent extractions, high-temperature heating and acid digestions that change the surface characteristics of the original PM. These results were compared to the analogous murine experiments. The results suggested that, at the same concentration of PM, the trend of toxicity and the posttreatment effects observed in BALB/c and human AM have a similar pattern. Altering the surface chemistry by removal of one or more PM components, such as through the various treatments conducted in this study, is sufficient to alter PM bioactivity in both human and murine AM in a similar manner. In addition, the human and murine models were compared with regard to in vitro cytotoxicity using PM_2.5 particles. The cytotoxic PM_2.5 effects were identical in both human and mouse models. Regression analysis revealed that the BALB/c mouse is a suitable model for PM cytotoxicity of AM as it is a good predictive model for the human AM responses.     

黄芪有效成分的药理作用与质量控制研究进展

黄芪是大宗药材,有效成分主要包括多糖类、皂苷类和黄酮类。多糖类成分是黄芪中含量最多的活性成分,具有提高免疫力、抗衰老、改善记忆力等药理作用;皂苷类成分具有抗炎、免疫调节、抗氧化等作用;黄酮类成分具有显著的抗氧化、抗衰老等作用。黄芪有效成分的质量控制方法以高效液相色谱法最为常用,根据不同有效成分的特性可选用不同的检测器;另外,红外光谱法、色谱-质谱联用技术等也是其质量控制的有效方法。综述黄芪有效成分的药理作用及其质量控制研究进展,明确黄芪有效成分的药理作用并为黄芪各有效成分的质量控制提供参考和依据。     

Health Effects of Airborne Particulate Matter: Do We Know Enough to Consider Regulating Specific Particle Types or Sources?

Researchers and regulators have often considered preferentially regulating the types of ambient airborne particulate matter (PM) most relevant to human health effects. While few would argue the inherent merits of such a policy, many believe there may not yet be enough information to differentially regulate PM species. New evidence, using increasingly sophisticated methodologies, has become available in the last several years, allowing more accurate assessment of exposure and resultant associations with specific types of PM, or PM derived from different sources. Such new studies may also allow differentiation of effects from different chemical components in the same study against the same health endpoints. This article considers whether this new evidence might be adequate to allow us to “speciate” PM types or sources by severity of health effects. We address this issue with respect to two widespread sources of PM, emissions from motor vehicles and coal-fired power plants. Emissions from less widespread sources, residual oil and steel/coking facilities, are also discussed in order to illustrate how health effects associated with such emissions might instead be associated with more widespread sources when accurate exposure information is unavailable. Based upon evaluation of studies and methodologies which appear to contain the most accurate information on exposure and response to important emissions, including variable local emissions, it is concluded that public health will likely be better protected by reduction of various vehicular emissions than by continued regulation of the total mass of fine PM (PM <2.5 μ m, or PM_2.5) as if all PM in this mode is equitoxic. However, the knowledge base is incomplete. Important remaining research questions are identified.     

Phenotypic Differences in Dextromethorphan Metabolism

Polymorphic differences in dextromethorphan metabolism were observed in three studies conducted in a total of 44 subjects (of Dutch origin) administered 60 mg dextromethorphan hydrobromide as an OROS tablet. Mean plasma dextromethorphan (DM) concentrations after a single dose and at steady state were 4–75 times higher in the poor metabolizers (PM) relative to the extensive metabolizers (EM). Following a single dose, the mean areas under the plasma concentration–time curve (AUC, 0–24 hr) of DM, total dextrorphan (DR), and total 3-hydroxymorphinan (HM) were 6.9-fold higher, 17.4-fold lower, and 11-fold lower, respectively, for the PM than for the EM. Correspondingly, steady-state AUC values were 52.8 times higher, 6.7 times lower, and 3.3 times lower for DM, total DR, and total HM, respectively, for the PM relative to the EM. Drug/metabolite ratios (DMR) for amounts excreted in the urine of DR and HM indicated polymorphism in O-demethylation of DM since DMR for PM was 352 and 338 times higher than that for EM for DR and HM, respectively. However, polymorphism in N-demethylation was not observed. Ratios of conjugated/free dextrorphan and 3-hydroxymorphinan excreted in the urine suggest also a lack of conjugative capacity in the PM, relative to the EM. The overall incidence of PM was 9.1% in this population.