Tacrolimus dosing in Chinese renal transplant recipients: a population-based pharmacogenetics study

被引:31
|
作者
Li, Liang [2 ]
Li, Chuan-Jiang [1 ]
Zheng, Lei [4 ]
Zhang, Yan-Jun [3 ]
Jiang, Hai-Xia [4 ]
Si-Tu, Bo [4 ]
Li, Zhong-Hai [1 ]
机构
[1] So Med Univ, Nanfang Hosp, Dept Organ Transplantat, Guangzhou 510515, Guangdong, Peoples R China
[2] So Med Univ, Dept Med Genet, Sch Basic Med Sci, Guangzhou 510515, Guangdong, Peoples R China
[3] Univ Cincinnati, Coll Pharm, Acad Hlth Ctr, Cincinnati, OH 45267 USA
[4] So Med Univ, Nanfang Hosp, Dept Clin Lab, Guangzhou 510515, Guangdong, Peoples R China
关键词
CYP3A5; Dosing model; Pharmacogenetics; Renal transplantation; Tacrolimus; SINGLE-NUCLEOTIDE POLYMORPHISMS; MDR1 GENETIC POLYMORPHISMS; CALCINEURIN INHIBITORS; DOSE REQUIREMENTS; ABCB1; POLYMORPHISMS; PHARMACOKINETICS; CYP3A5; IMPACT; HAPLOTYPES; TOXICITY;
D O I
10.1007/s00228-011-1010-y
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Objectives The aims of this study were to examine the effects of genetic and clinical factors on the maintenance dose of tacrolimus in patients following renal transplantation and to develop a tacrolimus-dosing model that could be combined with associated factors. Patients and methods This study included 142 renal transplant recipients who received tacrolimus as immunosuppressive agent. CYP3A5, MDR1 and NR1I2 gene polymorphisms were identified based on the SNaPshot assay. The relationship between the genetic and clinical factors and tacrolimus maintenance dose as well as between dose-corrected tacrolimus concentration was examined. Results CYP3A5 genotype, body weight, haematocrit, haemoglobin and total bilirubin significantly influenced the maintenance tacrolimus dose. The tacrolimus-dosing model derived from linear regression model accounted for 40.5% of total variations in the tacrolimus maintenance dose. Conclusions A pharmacogenetics-based dosing model has been developed for the prediction of the tacrolimus maintenance dose in renal transplant recipients. This model may be useful in helping clinicians prescribe the initial tacrolimus dose with greater safety and effectiveness.
引用
收藏
页码:787 / 795
页数:9
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