Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.
Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
Clin Pharmacol Ther. 2024 Dec;116(6):1513-1520. doi: 10.1002/cpt.3433. Epub 2024 Sep 5.
Recent advances have significantly enhanced our understanding of the role of membrane transporters in drug disposition, particularly focusing on their influence on pharmacokinetics, and consequently, pharmacodynamics. The relevance of these transporters in clinical pharmacology is well acknowledged. Recent research has also underscored the critical role of membrane transporters as targets in human diseases, including their involvement in rare genetic disorders. This review focuses on transporters for water-soluble B vitamins, such as thiamine, riboflavin, and biotin, essential cofactors for metabolic enzymes. Mutations in transporters, such as SLC19A3 (thiamine), SLC52A2, and SLC52A3 (riboflavin), and SLC5A6 (multiple B vitamins including pantothenic acid and biotin) are linked to severe neurological disorders due to their role in the blood-brain barrier, which is crucial for brain vitamin supply. Current treatments, mainly involving vitamin supplementation, often result in variable response. This review also provides a short perspective on the role of the transporters in the blood-cerebrospinal fluid barrier and highlights the potential development of pharmacologic treatments for rare disorders associated with mutations in these transporters.
近年来的进展极大地提高了我们对膜转运体在药物处置中的作用的理解，特别是关注它们对药代动力学的影响，进而对药效学的影响。这些转运体在临床药理学中的相关性得到了广泛认可。最近的研究还强调了膜转运体作为人类疾病靶点的关键作用，包括它们在罕见遗传疾病中的参与。本综述重点介绍了水溶性 B 族维生素转运体，如硫胺素、核黄素和生物素，它们是代谢酶的必需辅助因子。转运体（如 SLC19A3（硫胺素）、SLC52A2 和 SLC52A3（核黄素）以及 SLC5A6（多种 B 族维生素，包括泛酸和生物素）的突变与严重的神经紊乱有关，因为它们在血脑屏障中的作用对于大脑维生素供应至关重要。目前的治疗方法主要涉及维生素补充，通常会产生不同的反应。本综述还简要探讨了转运体在血脑脊液屏障中的作用，并强调了针对这些转运体突变相关罕见疾病的药物治疗的潜在发展。
