有限采样策略应用于中国器官移植患者霉酚酸暴露量估算的研究进展

Advances of limited sampling strategy used for estimating mycophenolic acid exposure in Chinese organ transplant patients

霉酚酸(mycophenolic acid, MPA)是一种抗代谢免疫抑制药,广泛应用于实体器官移植术后,其具有治疗窗窄、药动学个体差异大等特点,常常需要治疗药物监测(therapeutic drug monitoring, TDM)测定药-时曲线下面积(area under the concentration-time curve, AUC)指导个体化剂量调整。由于监测AUC需密集采样,TDM实施过程中呈现患者依从性差、监测耗时长、所需费用高等缺点。目前临床开展MPA的TDM多采用有限采样策略(limited sampling strategy, LSS)估算MPA-AUC。本文针对LSS估算中国实体器官移植患者MPA暴露量的研究进展进行综述,发现中国人群中MPA的LSS模型主要集中于成人肝、肾移植患者,大部分研究推荐3~4个点估算MPA-AUC;同时免疫抑制方案、霉酚酸剂型、检测方法、采血时间点等导致LSS公式存在差异,临床应用时应针对目标人群选择最佳公式进行MPA-AUC估算。

As an anti-metabolic proliferation immunosuppressant, mycophenolic acid(MPA) is widely applied for solid organ transplantation. It is characterized by a narrow therapeutic window and large inter-individual pharmacokinetics variabilities, requiring therapeutic drug monitoring(TDM) of the area under the concentration-time curve(AUC) for individualized therapy. However, the application of MPA TDM has been hindered by poor compliance, long monitoring time and high costs owing to intensive sampling. Nowadays limited sampling strategy(LSS) is generally employed for estimating MPA-AUC. In the present study, the application of LSS for estimating MPA exposure in Chinese solid organ transplantation patients was reviewed. The LSS studies of MPA in the Chinese population focused largely upon adult liver and kidney transplant patients and most studies recommend 3~4 points for calculating MPA-AUC. The discrepancies of LSS formulas have been attributed to the immunosuppressive regimens, MPA formulations, detection methods and sampling time. Thus the optimal formula should be selected for a target population to obtain a therapeutic range in clinical applications.