Factors Determining the Susceptibility of Fish to Effects of Human Pharmaceuticals,Environmental Science & Technology

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Factors Determining the Susceptibility of Fish to Effects of Human Pharmaceuticals
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2023-06-08 , DOI: 10.1021/acs.est.2c09576
Chrisna Matthee ₁ , Andrew Ross Brown ₁ , Anke Lange ₁ , Charles R Tyler ₁

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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.

中文翻译：

决定鱼类对人类药物影响的易感性的因素

在环境中检测到活性药物成分（API）的水平和频率不断增加，这引起了人们的极大关注，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利影响。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 及其生物转化产品对鱼类构成的潜在风险，同时仍尽量减少实验动物的使用。存在外在（环境和药物相关）和内在（鱼类相关）因素，这些因素使鱼类可能容易受到人类药物的影响，但不一定在非鱼类测试中被捕获。本批判性综述探讨了这些因素，特别关注鱼类中独特的生理过程，这些过程是药物吸收、分布、代谢、排泄和毒性（ADMET）的基础。重点包括鱼类生命阶段和物种对药物吸收的影响（A）通过多种途径;鱼类独特的血液 pH 值和血浆成分对药物分子在全身分布（D）的潜在影响;鱼的吸热性质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学如何影响不同排泄器官对 API 和代谢物排泄（E）的相对贡献。这些讨论有助于深入了解来自哺乳动物和临床研究的药物特性、药代动力学和药效学的现有数据可能有助于或可能无助于了解鱼类 API 的环境风险。

更新日期：2023-06-08

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