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

• Published in: European journal of clinical pharmacology 2011-08, Vol.67 (8), p.787-795
• Main Authors: Li, Liang, Li, Chuan-Jiang, Zheng, Lei, Zhang, Yan-Jun, Jiang, Hai-Xia, Si-Tu, Bo, Li, Zhong-Hai
• Format: Article
• Language: English
• Subjects: Adult; Asian people; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Bilirubin; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Body weight; China; Cohort Studies; Cytochrome P-450 CYP3A - genetics; Drug dosages; Drug Monitoring - methods; Gene polymorphism; Genotype & phenotype; Graft Rejection - prevention & control; Graft Survival - drug effects; Haplotypes; Hemoglobin; Humans; Immunosuppressive agents; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Kidney transplantation; Kidney Transplantation - adverse effects; Kidneys; Male; MDR1 protein; Medical Records; Medical sciences; Middle Aged; Models, Biological; Pharmacogenetics; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Polymorphism, Single Nucleotide; Receptors, Steroid - genetics; Regression analysis; Retrospective Studies; Tacrolimus; Tacrolimus - administration & dosage; Tacrolimus - blood; Tacrolimus - pharmacokinetics; Tacrolimus - therapeutic use; Transplants & implants
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-011-1010-y

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.