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  • 标题:The relationship between tacrolimus concentration-dose ratio and genetic polymorphism in patients subjected to renal transplantation
  • 本地全文:下载
  • 作者:Rančić, Nemanja ; Vavić, Neven ; Cikota-Aleksić, Bojana
  • 期刊名称:Vojnosanitetski pregled
  • 印刷版ISSN:0042-8450
  • 出版年度:2018
  • 卷号:75
  • 期号:2
  • 页码:147-153
  • DOI:10.2298/VSP151230329R
  • 出版社:Military Medical Academy, INI
  • 摘要:Background/Aim. Tacrolimus concentration-dose ratio as a potential therapeutic drug monitoring strategy was suggested to be used for the patients subjected to renal transplantation. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio, suggested to be used as a therapeutic drug monitoring strategy and the polymorphisms of genes encoding the most important enzymes, such as CYP3A5 and CYP3A4, as well as the transporter P-glycoprotein, for its metabolism and elimination. Methods. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real- Time PCR System by assessing allelic discrimination based on TaqMan® methodology. Results. Patients (n = 13) who were treated with less than 2 mg of tacrolimus/day (0.024 ± 0.006 mg/kg/day) had the tacrolimus concentration-dose ratio larger than 150 ng/mL/mg/kg. In this group, 84.62% patients had CYP3А5 *3*3 allele. All of these patients had CYP3А4 *1*1/*1*1B allele. Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant, while 69.23% of our patients had CC and CT gene variants. Conclusion. Tacrolimus concentration-dose ratio greater than 150 ng/mL/mg/kg is cut-off value in patients subjected to renal transplantation which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein.
  • 关键词:kidney transplantation; tacrolimus; dose-response relationship; drug; polymorphism; genetic
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