碳酸锂在双相障碍患者中个体化给药的研究进展

Research progress in individualized treatment of lithium carbonate in patients with bipolar disorder

碳酸锂作为一种心境稳定剂,是治疗双相障碍(BD)的一线药物。由于其治疗窗窄、个体差异大,疗效易受患者生理病理状态及药物相互作用的影响,且随着治疗药物监测(TDM)、群体药动学(PPK)及药物基因组学在碳酸锂个体化用药中辅助作用的日益凸显,如何更有效地优化碳酸锂的个体化用药备受关注。本文综述了近年来碳酸锂个体化治疗中TDM、PPK和药物基因组学的相关研究进展。由于受到患者病理生理状态的影响,不同人群的目标血锂浓度范围略有差异,为保证其疗效及安全性,需常规进行TDM。在不同人群中开展的PPK研究表明,用于优化锂盐治疗的相关预测因素包括体质量、瘦体质量、年龄、肾功能等。药物基因组学研究表明,FKBP5、ACP1、ADCY2等基因的单核苷酸多态性与患者的治疗反应差异相关。因此,在常规进行碳酸锂TDM的基础上,结合PPK和药物基因组学进行综合评估对碳酸锂的个体化治疗具有重要指导意义。

Lithium carbonate as a mood stabilizer,is the first-line treatment for bipolar disorder(BD).Due to the narrow treatment range and large individual response differences,physiological and pathological states and drug interactions can affect its therapeutic effect;as therapeutic drug monitoring(TDM),population pharmacokinetics(PPK)and pharmacogenomics play an increasingly important role in the individualized use of lithium carbonate,how to optimize the individualized use of lithium carbonate more effectively has attracted much attention.This paper reviewed the latest research progress of TDM,PPK and pharmacogenomics in the individualized treatment of lithium carbonate in recent years.Due to the influence of patients’pathophysiological status,the target blood concentration range of lithium among different populations was slightly different.To ensure its efficacy and safety,routine TDM was required.PPK studies conducted in different populations showed that the relevant predictors used to optimize lithium treatment included body mass,lean body mass,age and renal function,etc.Pharmacogenomics research showed that the single nucleotide polymorphisms of FKBP5,ACP1,ADCY2 and other genes were related to the difference of patients’treatment response.Therefore,on the basis of routine TDM for lithium carbonate,the comprehensive evaluation combined with PPK and pharmacogenomics is of great significance for the individual treatment of lithium carbonate.