Study on correlation between plasma concentration of cyclosporine injection and gene polymorphism in renal transplant patients / 药学实践杂志

ABSTRACT

Objective To investigate the clinical efficacy of cyclosporine injection in subclinical or critical treatment of renal transplant patients，and to establish an individualized dosage regimen of cyclosporine injection by studying the effects of nine single nucleotide polymorphisms related to the pharmacokinetics of cyclosporine on the dose-adjusted trough concentration (C0/D′) of cyclosporine injection. Methods Blood samples and clinical data of 144 adult renal transplant patients who used cyclosporine injection were collected and recorded, then, their genotypes of CYP3A4*18B, CYP3A5*3, ABCB1 (C1236T, G2677T/A, C3435T), POR*28, PXR (C5705T, C39823T) and NFKB1-94 ins/del ATTG were determined by Sequenom MassARRAY® SNP methods. Then, the discrepancies of cyclosporine injection’s C0/D′ among the patients with different genotypes was compared and an individualized dosage regimen based on gene polymorphism of cyclosporine injection was established by using multivariate regression analysis. Results Cyclosporine injection improved serum creatinine level by 68.8% in renal transplant patients with subclinical or critical rejection, and the steady-state plasma concentration was (189.50±38.56) ng/ml. The CYP3A4*18B gene polymorphism was significantly correlated to C0/D' of cyclosporine injection, and the C0/D' of patients with *1/*1 genotype was significantly higher than patients of *18B/*18B genotype; but CYP3A5*3, ABCB1(C1236T, G2677T/A, C3435T), PXR C5705T, PXR C39823T, NFKB1-94 ins/del ATTG and POR*28 gene polymorphisms were not significantly correlated to C0/D' of cyclosporine injection. In the final regression model, hemoglobin and CYP3A4*18B gene polymorphisms were significantly correlated to C0/D' of cyclosporine injection. Conclusion Cyclosporine injection can effectively improve the serum creatinine level in patients with subclinical or critical rejection; CYP3A4*18B gene polymorphism is significantly correlated to C0/D' of cyclosporine injection.