Understanding mechanisms underlying an increased sensitivity of central nervous system to therapeutic compounds with decreased renal function for dose optimization and individualizing treatment

已有研究表明，药物代谢酶的肝脏表达随着肾功能下降而改变。当肾功能受损时，脉络膜丛电解质转运蛋白的表达也会发生变化。这些发现表明，中枢神经系统对治疗性化合物的敏感性增加是由药物对中枢神经系统的处置增加引起的。增加的药物处置似乎是肝脏酶表达改变的结果，与中枢神经系统的稳态紊乱以及脉络膜丛电解质转运蛋白的表达改变有关。

It has been elucidated that the hepatic expression of the drug metabolizing enzyme is altered with a decreased renal function. The expression of electrolyte transporter in choroid plexus also varies when renal function is impaired. These findings suggest that an increased sensitivity of central nervous system to therapeutic compounds is caused by the increase in the drug disposition to central nervous system. The increased drug disposition seems to be a result of an altered hepatic enzyme expression in conjunction with a perturbed homeostasis of central nervous system with an altered choroid plexial expression of electrolyte transporters.