他克莫司在儿童肾病综合征群体中的治疗药物监测

Therapeutic Drug Monitoring of Tacrolimus in Children with Nephrotic Syndrome

他克莫司是肾病综合征患儿的二线治疗药物。然而其治疗窗狭窄,血药浓度在个体间和个体内的差异较大,为临床安全合理应用带来了挑战。因此,笔者回顾了国内外关于他克莫司血药浓度的影响因素及其在肾病综合征患儿中应用的相关研究,探讨其在治疗过程中应维持的目标浓度。他克莫司的药动学过程受到了生理病理、联合用药、饮食和药物代谢酶遗传多态性等多种因素的影响。他克莫司的最佳血药浓度范围存在着争议,关于谷浓度与疗效及不良反应相关性的研究较少,但近几年不断有研究指出,低于5~10 ng·mL^(-1)的目标谷浓度对于肾病综合征的治疗仍然有效。考虑到他克莫司血药浓度影响因素众多,临床应通过治疗药物监测以调整给药剂量,但关于目标治疗浓度仍有待质量高的临床试验进一步研究。

Tacrolimus(TAC),a calcineurin inhibitor,has been widely used as a second-line immunosuppressant for the treatment of children with nephrotic syndrome.However,the narrow therapeutic window and the wide inter-individual pharmacokinetic(PK)variability of TAC are hidden troubles for clinical application.The published articles regarding the contributing factors of TAC plasma concentration and the application of TAC in children with nephrotic syndrome were reviewed,and the ideal range of TAC concentration was discussed.Oral TAC is rapidly absorbed,while the bioavailability is low.The PK is affected by physiopathology,co-medications,diet,genetic polymorphism of drug metabolizing enzymes and other factors.Studies on the correlation between TAC concentration and efficacy were few,and the optimal range of concentration is controversial.Recent years,it has been pointed out that the target valley concentration below 5-10 ng·mL^(-1) is still effective for the treatment of nephrotic syndrome.Therapeutic drug monitoring is still needed to adjust the dose of the TAC,while the target therapeutic concentration remains to be further studied in high quality clinical trials.