Scholarlink

The extent of binding to human serum albumin (HSA) has a huge impact on a drug’s pharmacokinetics and pharmacodynamics. Only the unbound fraction can interact with a target, and distribution and excretion are influenced by protein binding. This must be considered with the drug dose regimen. Because even enantiomers of a racemic drug may have different HSA binding, the extent of HSA binding must be carefully determined. These are the reasons why we studied racemic ketamine as well as each of its enantiomers separately with respect to HSA binding (Schmidt S, Holzgrabe U. Eur J Pharm Sci 192:106640, 2024). Importantly, the isomers and the racemate were found to show a very similar extent of binding: The bound fraction was 71.2% for R-ketamine-ketamine, 64.9% for S- ketamine, and 66.5% for the racemic mixture. According to ultrafiltration analysis, ketamine is a rather weak ligand to HSA. Our study reveals that the racemate and both isomers do not show clinically relevant differences in binding behavior to HSA.

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Is There a Difference in Ketamine Enantiomer Binding to Human Serum Albumin?

  • 实验方案

  • 发表日期：

    2025年

查看全文
  • Ulrike Holzgrabe,
  • Sebastian Schmidt

摘要

The extent of binding to human serum albumin (HSA) has a huge impact on a drug’s pharmacokinetics and pharmacodynamics. Only the unbound fraction can interact with a target, and distribution and excretion are influenced by protein binding. This must be considered with the drug dose regimen. Because even enantiomers of a racemic drug may have different HSA binding, the extent of HSA binding must be carefully determined. These are the reasons why we studied racemic ketamine as well as each of its enantiomers separately with respect to HSA binding (Schmidt S, Holzgrabe U. Eur J Pharm Sci 192:106640, 2024). Importantly, the isomers and the racemate were found to show a very similar extent of binding: The bound fraction was 71.2% for R-ketamine-ketamine, 64.9% for S- ketamine, and 66.5% for the racemic mixture. According to ultrafiltration analysis, ketamine is a rather weak ligand to HSA. Our study reveals that the racemate and both isomers do not show clinically relevant differences in binding behavior to HSA.