大家好，文献翻译带练的文本内容第一时间法评论区，然后每两期视频出一期文本专栏。
文献翻译带练11 bioequivalence
the drug product’s efficacy depends on the amount of the active moiety which becomes available at the site of action and how rapidly this process takes place. The term bioavailability was then officially introduced by the FDA to describe both the extent and rate of drug arrival in the systemic circulation, while bioequivalence refers to comparative bioavailability studies.Since then, BE assessment relies on the assumption that the therapeutic effect is a function of concentration of the active moiety in the systemic circulation.The regulatory authorities worldwide consider two drug products to be bioequivalent if they contain the same active substance, are at the same molar dose, and their rate and extent of absorption are similar to ensure comparable in vivo performance.
参考答案：药物的功效取决于作用部位可获得的活性部分的数量以及这个过程发生的速度。随后，FDA(美国食品药物监督管理局)正式引入了生物利用度一词，用来描述药物进入体循环的程度和速度，而生物等效性是指比较生物利用度研究。从那时起，生物等效性的评估就依赖于这样一个假设，即治疗效果是体循环中活性成分浓度的函数。世界各地的监管机构认为，如果两种药品含有相同的活性物质，具有相同的摩尔剂量，并且它们的吸收速率和程度相似，以确保体内性能相当，那么它们就是生物等效的。
The role of drug metabolites (M) in the determination of BE represents another unresolved issue in the field of BE.Usually, BE studies are carried out focusing only on the measurement of the parent drug (P). The latter relies on the fact that the concentration–time profile of P is more sensitive to detect differences in formulation performance than M.However, there are situations where metabolite data could exert a significant role in BE assessment. Such cases include the conditions where the parent drug levels in biological fluids are low to allow an accurate analytical measurement, P is an inactive pro-drug or is unstable in the biological fluids, and when M contributes significantly to the net activity with a nonlinear underlying PK system.
参考答案：药物代谢物在生物等效性测定中的作用是生物等效性领域中另一个尚未解决的问题。通常，生物等效性研究只关注母体药物(原型药物)的测量。后者基于母体药物的浓度-时间曲线相较于药物代谢物对检测方法特异性差异(注：这里我采取意译了，直译不知道说的啥玩意儿)更敏感。然而，在某些情况下，代谢物数据可能在生物等效性评估中发挥重要作用。这种情况包括生物样品中的母体药物水平较低，无法进行准确的分析测量，母体药物是一种非活性前药或生物样本中不稳定，以及药物代谢物对一个非线性药代动力学系统的净活性有显著贡献的情况。
文献翻译带练12 Therapeutic drug monitoring (TDM)
Clinical pharmacokinetics is the study of the relationships between drug-dosing regimens and drug concentration-time profiles. This means the study of the drug’s absorption,distribution, metabolism, and elimination (ADME) profiles. Therapeutic drug monitoring (TDM) is the measurement of drug concentration in biological fluids to determine the drug dose achieving a pre-defined target level for a patient. This technique necessitates that a relationship between concentration and effect to be demonstrated as for some special agents.Measures of exposure include the area under the plasma concentration-time curve (AUC), time above a threshold concentration, maximum concentration (Cmax), and trough concentration. TDM can correct for most of PK variability, consequently reducing the variability in response.
参考答案：临床药代动力学是研究给药方案和药物浓度-时间曲线之间的关系。这意味着研究药物的吸收、分布、代谢和排泄的概况。治疗性药物监测是测量生物样本中的药物浓度，以确定达到病人预定目标水平的药物剂量。该技术需要证明一些特殊药物的浓度和药效之间的关系。测量参数(exposue直译太别扭了)包括血浆浓度-时间曲线下的面积(AUC)，超过阈值浓度的时间，最大浓度(Cmax)和谷浓度。治疗性药物监测可以纠正药代动力学的大部分变异性，从而减少响应的变异性。
The selection of an appropriate therapy and dosing regimen is a significant challenge in the treatment of cancer. Although there are recommended standardized chemotherapy protocols for some types of cancer, protocol changes that usually only occur after large clinical trials demonstrate improvements and individual patients often require dose modifications (amount or interval) or delays in dose administration as toxicities arise. In other areas of medicine, therapeutic drug monitoring is commonly and successfully used to ensure appropriate drug exposure and to limit dose-related toxicities. Currently, the wide pharmacokinetic variability of cytotoxic chemotherapies is addressed clinically by the use of body surface area to determine drug doses; however, this is outdated and demonstrably ineffective for this purpose.
参考答案：在癌症的治疗中，选择一个适当的治疗和剂量方案是一个重大的挑战。虽然对于某些类型的癌症有推荐的标准化化疗方案，但方案的改变通常只发生在大型临床试验表明有所改善之后，而且由于毒性的出现，个别患者往往需要修改剂量(数量或间隔)或延迟给药。在其他医学领域，治疗性药物监测通常成功地用于确保适当的药物暴露和仅限于剂量相关的毒性。目前，细胞毒性化疗的广泛药代动力学差异在临床上是通过使用体表面积来确定药物剂量来解决的。然而，这种方法是过时的，显然无法达到目的。
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