Cai Ningfang, Li Bifeng, Huang Xiaohong, Xu Kezhen, Feng Huiping, Cheng Zeneng, Zhu Lijun, Zheng Liyun, Luo Xi
Pharmazie. 2015 Dec;70(12):815-8.
An endogenous CYP3A4 biomarker for in vivo metabolism of cyclosporine should be useful for optimizing individual dosage. We aimed to investigate if the combined ratio of endogenous 6β-hydroxycortisol and 6β-hydroxycortisone to cortisol and cortisone (HOM) in urine could be used as an endogenous probe for the prediction of cyclosporine dosage requirements in renal transplant recipients. 54 medically stable kidney transplant recipients participated in this study. Morning spot blood and urine samples were gathered. The multiple regression analysis including urinary HOM and body mass index accounted for 73.1% of variability in blood concentration/dose ratio (C/D) of cyclosporine, in which urinary HOM and body mass index contributed 64.9% and 8.2%, respectively. Based on the present approach, individual dosage regimen of CsA could be acquired without therapeutic drug monitoring and the results showed that all of the observed stable doses of CsA were within the predicted range during different post-operative periods. In summary, there is a significant relationship between endogenous CYP3A4 biomarker (assessed by urinary HOM) and in vivo metabolism of cyclosporine in renal transplant recipients. Urinary HOM and body mass index are important predictors of cyclosporine metabolism. Our findings provide clinical implications that the predictive algorithm based on a simple, safe and non-invasive CYP3A4 phenotyping can be anticipated.
一种用于环孢素体内代谢的内源性CYP3A4生物标志物应有助于优化个体剂量。我们旨在研究尿液中内源性6β-羟基皮质醇和6β-羟基可的松与皮质醇和可的松的联合比值（HOM）是否可作为预测肾移植受者环孢素剂量需求的内源性探针。54名病情稳定的肾移植受者参与了本研究。采集了晨尿和血样。包括尿HOM和体重指数的多元回归分析解释了环孢素血药浓度/剂量比（C/D）变异的73.1%，其中尿HOM和体重指数分别贡献了64.9%和8.2%。基于目前的方法，无需治疗药物监测即可获得环孢素的个体给药方案，结果显示，在术后不同时期，所有观察到的环孢素稳定剂量均在预测范围内。总之，肾移植受者体内内源性CYP3A4生物标志物（通过尿HOM评估）与环孢素的体内代谢之间存在显著关系。尿HOM和体重指数是环孢素代谢的重要预测指标。我们的研究结果具有临床意义，基于简单、安全且无创的CYP3A4表型分析的预测算法值得期待。
