Biosciences, University of Exeter, Exeter, Devon EX4 4QD, United Kingdom.
Environ Sci Technol. 2023 Jun 20;57(24):8845-8862. doi: 10.1021/acs.est.2c09576. Epub 2023 Jun 8.
The increasing levels and frequencies at which active pharmaceutical ingredients (APIs) are being detected in the environment are of significant concern, especially considering the potential adverse effects they may have on nontarget species such as fish. With many pharmaceuticals lacking environmental risk assessments, there is a need to better define and understand the potential risks that APIs and their biotransformation products pose to fish, while still minimizing the use of experimental animals. There are both extrinsic (environment- and drug-related) and intrinsic (fish-related) factors that make fish potentially vulnerable to the effects of human drugs, but which are not necessarily captured in nonfish tests. This critical review explores these factors, particularly focusing on the distinctive physiological processes in fish that underlie drug absorption, distribution, metabolism, excretion and toxicity (ADMET). Focal points include the impact of fish life stage and species on drug absorption (A) via multiple routes; the potential implications of fish's unique blood pH and plasma composition on the distribution (D) of drug molecules throughout the body; how fish's endothermic nature and the varied expression and activity of drug-metabolizing enzymes in their tissues may affect drug metabolism (M); and how their distinctive physiologies may impact the relative contribution of different excretory organs to the excretion (E) of APIs and metabolites. These discussions give insight into where existing data on drug properties, pharmacokinetics and pharmacodynamics from mammalian and clinical studies may or may not help to inform on environmental risks of APIs in fish.
越来越多的活性药物成分 (API) 在环境中被检测到，而且其浓度和频率也在不断增加，这引起了人们的高度关注，尤其是考虑到它们可能对鱼类等非目标物种产生潜在的不良影响。由于许多药物缺乏环境风险评估，因此需要更好地定义和理解 API 及其生物转化产物对鱼类可能造成的潜在风险，同时尽量减少实验动物的使用。有外在的（与环境和药物相关）和内在的（与鱼类相关）因素使鱼类容易受到人类药物的影响，但这些因素在非鱼类测试中不一定被捕捉到。本批判性评论探讨了这些因素，特别是重点关注鱼类独特的生理过程，这些过程是药物吸收、分布、代谢、排泄和毒性（ADMET）的基础。关注的焦点包括鱼类生活阶段和物种通过多种途径对药物吸收（A）的影响；鱼类独特的血液 pH 值和血浆组成对药物分子在体内分布（D）的潜在影响；鱼类的恒温特性以及其组织中药物代谢酶的不同表达和活性如何影响药物代谢（M）；以及它们独特的生理机能如何影响不同排泄器官对 API 和代谢物排泄（E）的相对贡献。这些讨论深入了解了从哺乳动物和临床研究中获得的关于药物特性、药代动力学和药效学的现有数据在多大程度上可以帮助了解 API 在鱼类中的环境风险，或者在多大程度上无法提供帮助。
