新型双食欲素受体拮抗剂上市药物的药动学与药效学研究进展

Advances in pharmacokinetic and pharmacodynamic studies of novel dual orexin receptor antagonists on the market

食欲素是一种由下丘脑合成和分泌的神经肽,食欲素及其受体的相互作用参与睡眠活动的中枢生理调节。双食欲素受体拮抗剂是一种具有新型药理作用机制的失眠治疗药物,该类药物通过阻断食欲素与食欲素受体结合发挥促眠作用,其选择性高,不良反应较少。目前已有3种双食欲素受体拮抗剂达利雷生、苏沃雷生和莱博雷生获批上市,用于治疗以入睡困难和睡眠维持困难为特征的成人失眠。本文从药动学和药效学角度对这3种双食欲素受体拮抗剂进行综述,总结三者的药物处置(吸收、分布、代谢、排泄)、药物相互作用、临床疗效、不良反应和药物滥用等,为失眠症患者的临床治疗提供参考和用药证据。

Orexin is a neuropeptide synthesized and secreted by hypothalamus,and the interaction between orexin and its receptors influences the central physiological regulation of sleep activities.Dual orexin receptor antagonists are novel treatment for insomnia of new pharmacological mechanism,which play a role in promoting sleep by blocking the combination of orexin and orexin receptors,with high selectivity and few adverse reactions.At present,three dual orexin receptor antagonists,daridorexant,suvorexant,and lemborexant have been approved for marketing,indicated for the treatment of adult patients with insomnia characterized by difficulties with sleep onset and/or sleep maintenance.This article reviewed the three orexin receptor antagonists from the perspectives of pharmacokinetics and pharmacodynamics,summarized their characteristics in drug disposition(absorption,distribution,metabolism,and excretion),drug-drug interactions,drug function mechanism,clinical efficacy,adverse reactions,and drug abuse,etc.,so as to provide reference and evidence for their application in treatment of insomnia patients.