van Gelder Teun, Berden Jo H M, Berger Stefan P
Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Nephrol Dial Transplant. 2015 Apr;30(4):560-4. doi: 10.1093/ndt/gfu184. Epub 2014 May 8.
Mycophenolic acid (MPA) has become the cornerstone in the treatment of lupus nephritis. However, response rates are still far from ideal in clinical trials. Uncertainty exists regarding the correct dosing of MPA, and the recommended doses vary between recently published guidelines. Side effects are an additional problem resulting in frequent dose reduction and possible suboptimal exposure.In this review, we discuss the large variability between patients in drug exposure to MPA and the evidence for a relationship between drug exposure and efficacy in lupus nephritis. Methods for drug monitoring of MPA are discussed, and based on the current literature, we suggest as potential target levels a pre-dose level of 3.0 mg/L and an area under the concentration-versus-time curve between 35 and 45 mg h/L.Therapeutic drug monitoring may improve response rates in lupus nephritis by preventing low exposure and at the same time may reduce unnecessary side effects in patients who have high drug exposure with standard dose MPA. We specifically advise assessment of MPA drug exposure early after start of treatment and before concluding that treatment with MPA has failed.
霉酚酸(MPA)已成为狼疮性肾炎治疗的基石。然而,在临床试验中,其缓解率仍远不理想。MPA的正确剂量存在不确定性,最近发布的指南中推荐剂量也各不相同。副作用是另一个问题,常导致剂量频繁减少以及可能的暴露不足。在本综述中,我们讨论了患者间MPA药物暴露的巨大差异,以及狼疮性肾炎中药物暴露与疗效之间关系的证据。讨论了MPA的药物监测方法,并基于当前文献,我们建议潜在的目标水平为给药前水平3.0mg/L,浓度-时间曲线下面积在35至45mg·h/L之间。治疗药物监测可通过防止暴露不足来提高狼疮性肾炎的缓解率,同时可减少接受标准剂量MPA时药物暴露高的患者的不必要副作用。我们特别建议在治疗开始后早期以及在判定MPA治疗失败之前评估MPA药物暴露情况。