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.
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.
Authors: Pierre Wallemacq; Victor W Armstrong; Merce Brunet; Vincent Haufroid; David W Holt; Atholl Johnston; Dirk Kuypers; Yannick Le Meur; Pierre Marquet; Michael Oellerich; Eric Thervet; Burkhand Toenshoff; Nas Undre; Lutz T Weber; Ian S Westley; Michel Mourad Journal: Ther Drug Monit Date: 2009-04 Impact factor: 3.681
Authors: Hong-Guang Xie; Alastair J J Wood; Richard B Kim; C Michael Stein; Grant R Wilkinson Journal: Pharmacogenomics Date: 2004-04 Impact factor: 2.533
Authors: Eric Thervet; Dany Anglicheau; Barry King; Marie-Hélène Schlageter; Bruno Cassinat; Philippe Beaune; Christophe Legendre; Ann K Daly Journal: Transplantation Date: 2003-10-27 Impact factor: 4.939
Authors: Diego Alberto C Cusinato; Riccardo Lacchini; Elen A Romao; Miguel Moysés-Neto; Eduardo B Coelho Journal: Br J Clin Pharmacol Date: 2014-08 Impact factor: 4.335
Authors: L Rojas; I Neumann; M José Herrero; V Bosó; J Reig; J Luis Poveda; J Megías; S Bea; S F Aliño Journal: Pharmacogenomics J Date: 2014-09-09 Impact factor: 3.550