文献翻译带练15 PK-PD model
Traditionally, therapeutic drug monitoring relies largely on pharmacokinetic (PK) parameters, measuring the handling of the drug by the organism. Although PK gives reliable information on drug absorption, distribution, metabolism, and excretion and allows in some cases the correlation of drug concentration with (side) effects, a number of problems remain. In particular, PK does not directly quantify the pharmacological effects on physiologically relevant immune cells. Moreover, the interindividual variability of susceptibility to immunosuppressant drugs is not fully accounted for by PK measurements. The same drug dose and equal exposure in different individuals can lead to different biologic and clinical outcomes, thereby limiting the correlation between drug exposure and efficacy.
参考答案：传统上，治疗性药物监测主要依赖于药代动力学参数，测量机体对药物的处理。虽然药代动力学提供了药物吸收、分布、代谢和排泄的可靠信息，并允许在某些情况下药物浓度与药效或副作用的相关性(注：这里文献原文就是(side) effect，可理解为effect or side effect)，但仍存在一些问题。特别是，药代动力学并没有直接量化对生理相关免疫细胞的药理作用。此外，对免疫抑制药物的个体间易感性的差异并不能完全由药代动力学检测来解释。在不同的个体中，相同的药物剂量和相同的暴露可能导致不同的生物学和临床结果，从而限制了药物暴露和疗效之间的相关性(注：药物暴露可理解为药物的血药浓度)。
Antibiotic pharmacodynamics (PD) describes the impact of an antimicrobial agent on a target pathogen and is based on the drug’s pharmacokinetics (PK) and microbiologic activity toward that pathogen, together with the pathogen’s susceptibility to the drug.Patient or host factors play an important role in antibiotic PD by affecting drug PK and patient susceptibility to infection. The 3 PK/PD parameters commonly used to predict antibiotic efficacy are (1) the ratio of maximum serum concentration to the minimum inhibitory concentration (MIC) (Cmax/MIC); (2) the ratio of the area under the plasma concentration versus time curve (AUC) versus MIC (AUC/MIC) and (3) the duration of the dosing interval that plasma concentrations exceed the MIC (T＞MIC).
参考答案：抗生素药效学描述了抗菌药对目标病原体的影响，并基于药物的药动学和针对该病原体的微生物活性，以及病原体对药物的敏感性。患者或宿主因素通过影响药物的药动学和患者对感染的易感性，在抗生素药效学中发挥重要作用。常用来预测抗生素疗效的3个PK/PD参数为(1)最大血清浓度与最小抑菌浓度的比值(Cmax/MIC);(2)血药浓度-时间曲线下面积(AUC)与最小抑菌浓度的比值(AUC/MIC);(3)血药浓度超过最小抑菌浓度的给药间隔时间(T>MIC)。
文献翻译带练16 Preclinical pharmacokinetic studies of innovative drugs
Pharmacokinetics are the study of the movement of drug substances in living organisms using delineative models and mathematical rate equations to describe the absorption, distribution, metabolism or degradation, and elimination(clearance) of drugs from the body. Pharmacokinetic assessments have become an essential component in the preclinical development and translation of nanomaterial based drug delivery systems and are routinely studied in preclinical and clinical nanomaterials literature. The motivations for leveraging nanoscale materials for drug delivery are rooted in the distinct kinetic behaviours of nanomaterial-based drugs in vivo, such as improved delivery of encapsulated drug into target tissues (e.g., tumours) and reduced toxicities associated with off-target drug accumulation (e.g.,cardiotoxicity, nephrotoxicity cutaneous phototoxicity, etc.)
参考答案：药代动力学是研究药物在生物体中的运动，使用描述模型和数学速率方程来描述药物的吸收、分布、代谢或降解，以及药物从体内的排泄(清除)。药代动力学评估已经成为基于纳米材料的药物传递系统临床前开发和转化的重要组成部分，在临床前和临床纳米材料文献中经常进行研究。利用纳米材料给药的动机是基于纳米材料的药物在体内的独特动力学行为，如改进了包裹药物到目标组织(如肿瘤)的输送，以及减少与脱靶药物积累相关的毒性(如心脏毒性、肾毒性、皮肤光毒性等)
Antibody–drug conjugates(ADC) are an emerging class of biopharmaceuticals changing the landscape of targeted chemotherapy. These conjugates combine the target specificity of monoclonal antibodies with the anti-cancer activity of small-molecule therapeutics.Briefly, the monoclonal antibody moiety of the ADC will bind to the target antigen on the surface of cells.The entire ADC complex is then internalized, the conjugated drug is released, and the cell is killed by the cytotoxic effect of the conjugated drug. This strategy has also been employed for overcoming multidrug resistance in target cells. Understanding the pharmacokinetics and pharmacodynamics of antibody–drug conjugates and the development of pharmacokinetic/pharmacodynamic models is indispensable.
参考答案：抗体偶联药物是一类新兴的生物药物，改变了靶向化疗的前景。这些偶联物结合了单克隆抗体的靶向特异性和小分子疗法的抗癌活性。简单地说，ADC的单克隆抗体部分会与细胞表面的目标抗原结合。然后，整个ADC复合物被内吞，偶联药物被释放，细胞被偶联药物的细胞毒性作用杀死。这一策略也被用于克服靶细胞的多药耐药性。了解抗体-药物偶联物的药代动力学和药效学以及建立药代动力学-药效学结合模型是必不可少的。