Study of Tacrolimus Used for Pediatric Patients With Nephrotic Syndrome Based on Pharmacogenomics and Metabonomics

Tacrolimus is recommended to be the first line therapeutic medication within the several immunosuppressive agents when treating refractory pediatric nephrotic syndrome, because of its definite efficacy and low toxicity. But there are still some key problems which hinder the using of tacrolimus in clinic, such as its narrow therapeutic widow, great individual difference of pharmacokinetics. Routine therapeutic drug monitoring(TDM) is needed in practice. But the disadvantage of TDM is hysteresis, which could lead to treatment failure or toxicity. To find out the reasons of great pharmacokinetic difference between patients and find out the individual proper dosage before administration are important for the clinical using of tacrolimus. It is hot in research of tacrolimus in organ transplant field, such as the association between gene polymorphisms of cytochrome P-450 3A4, 3A5 and multiple drug resistant gene(MDR1) and concentration of tacrolimus. However, there is few study about pharmacogenomics and metabonomics of tacrolimus in patients of nephrotic syndrome. The aim is to study the relationships between pharmacogenomics, metabonomics of tacrolimus and its efficacy, toxicity and blood concentration in patients of nephrotic syndrome, to find out the exact dosage before administration, to provide reference to individual drug administration.