Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
Providence Health Care, Vancouver, BC, Canada.
Clin Pharmacokinet. 2017 Sep;56(9):1015-1031. doi: 10.1007/s40262-017-0521-9.
Leflunomide is an immunosuppressive drug with in vitro and initial observational evidence of antiviral activity against BK virus (BKV), a pathogen that causes opportunistic infection upon reactivation in renal transplant recipients. Leflunomide is considered an ancillary option to immunosuppression reduction in the management of BKV reactivation. Plasma or blood concentrations of teriflunomide, the active metabolite of leflunomide, are commonly monitored because of high leflunomide doses being used, known inter-individual variability in pharmacokinetics, and hepatotoxicity risk. However, the utility of clinical pharmacokinetic monitoring for leflunomide is as yet unclear. A literature search of MEDLINE (1946-December 2016), EMBASE (1974-December 2016), the CENTRAL database, and Google Scholar was performed to identify relevant English-language articles. Further articles were identified from references in relevant literature. A previously published 9-step decision-making algorithm was used to assess the available literature and determine the utility of clinical pharmacokinetic monitoring for leflunomide. Teriflunomide is readily measurable in the plasma or blood, but a clear relationship between concentration and efficacy or toxicity is lacking, and its therapeutic range is not well-established. Efficacy and toxicity endpoints such as renal function and BKV clearance can be readily assessed without measuring teriflunomide concentrations. Pharmacokinetic parameters are affected by genetic polymorphisms in cytochrome P450 CYP2C19 and ABCG2 genes. Therefore, routine clinical pharmacokinetic monitoring of leflunomide cannot be recommended based on current available evidence. However, it may provide clinical benefit in difficult situations when patients demonstrate a lack of therapeutic response or exhibit signs of drug toxicity.
来氟米特是一种免疫抑制剂，具有体外和初步观察到的抗 BK 病毒（BKV）的抗病毒活性证据，BKV 是一种病原体，在肾移植受者中重新激活时会引起机会性感染。来氟米特被认为是减少免疫抑制治疗 BKV 再激活的辅助选择。由于使用了高剂量的来氟米特、药代动力学个体间的高度变异性以及肝毒性风险，通常监测来氟米特的活性代谢产物特立氟胺的血浆或血液浓度。然而，来氟米特临床药代动力学监测的实用性尚不清楚。通过 MEDLINE（1946 年-2016 年 12 月）、EMBASE（1974 年-2016 年 12 月）、CENTRAL 数据库和 Google Scholar 进行文献检索，以确定相关的英文文献。从相关文献中的参考文献中进一步确定了其他文章。使用先前发表的 9 步决策算法来评估现有文献，并确定来氟米特临床药代动力学监测的实用性。特立氟胺在血浆或血液中易于测量，但缺乏浓度与疗效或毒性之间的明确关系，其治疗范围也尚未确定。无需测量特立氟胺浓度即可轻易评估肾功和 BKV 清除等疗效和毒性终点。药代动力学参数受细胞色素 P450 CYP2C19 和 ABCG2 基因的遗传多态性影响。因此，根据目前的可用证据，不能推荐常规临床药代动力学监测来氟米特。但是，当患者表现出缺乏治疗反应或出现药物毒性迹象时，它可能会在困难的情况下提供临床益处。
