Goldman Modan R, Molina-Castro Mariel, Etkins Jumar C, Koide Theodore L, Ramchandani Vijay A, Plawecki Martin H, Mennella Julie A, Pepino Marta Yanina
Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Champaign, Illinois, United States.
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, Illinois, United States.
Physiol Rev. 2025 Oct 1;105(4):2501-2535. doi: 10.1152/physrev.00053.2024. Epub 2025 Jul 10.
Globally, alcohol is the most widely used psychoactive drug and a leading cause of premature death among individuals aged 15-49 years. Understanding the absorption, distribution, metabolism, and excretion of alcohol in the human body, otherwise known as alcohol pharmacokinetics, is essential for predicting its behavioral effects and toxic consequences. This review examines the evolutionary origins of alcohol consumption and metabolism, focusing on the activity of alcohol dehydrogenase enzymes across species, which serve as key catalysts in alcohol oxidation. It also highlights recent advances in understanding central alcohol metabolism and updates on the potential clinical significance of nonoxidative pathways of alcohol metabolism and endogenous alcohol production, particularly in the context of liver disease. In addition, the review inspects factors that modulate alcohol metabolism, including genetic polymorphisms, biological sex, food intake, women's reproductive status, and clinical interventions such as medications and metabolic surgeries. Understanding these sources of variability in alcohol metabolism is crucial for identifying individual risk factors and tailoring strategies to reduce alcohol-related harm. This comprehensive review offers a current perspective on alcohol pharmacokinetics, valuable insights into its implications for health, behavior, and potential innovative therapeutic targets.
在全球范围内，酒精是使用最广泛的精神活性药物，也是15至49岁人群过早死亡的主要原因。了解酒精在人体内的吸收、分布、代谢和排泄情况，即酒精药代动力学，对于预测其行为影响和毒性后果至关重要。本综述探讨了酒精消费和代谢的进化起源，重点关注跨物种酒精脱氢酶的活性，这些酶是酒精氧化的关键催化剂。它还强调了在理解中枢酒精代谢方面的最新进展，以及酒精代谢非氧化途径和内源性酒精产生的潜在临床意义的更新，特别是在肝病背景下。此外，该综述考察了调节酒精代谢的因素，包括基因多态性、生物性别、食物摄入、女性生殖状态以及药物和代谢手术等临床干预措施。了解酒精代谢中这些变异性来源对于识别个体风险因素和制定减少酒精相关危害的策略至关重要。这篇全面的综述提供了关于酒精药代动力学的当前观点，对其对健康、行为的影响以及潜在的创新治疗靶点提供了有价值的见解。
