Pharmacogenetic-based strategy using de novo tacrolimus once daily after kidney transplantation: prospective pilot study.
The once daily tacrolimus formulation (Tac-OD) has been associated with better patient adherence and low variability in exposure. Patients carrying the CYP3A5*1 allele show accelerated clearance of Tac. Authors prospectively evaluate a simplified strategy for Tac-OD administration.



After grafting, 151 patients were divided into four groups and received a daily dose calculated according to CYP3A5 genotypes and unchanged for the first 3 days: CYP3A5*3/*3: 0.20 mg/kg/day, CYP3A5*3/*3: 0.25 mg/kg/day, CYP3A5*1/*3: 0.30 mg/kg/day and CYP3A5*1/*1: 0.35 mg/kg/day. The dose was adaptated on day 4 and remained unchanged a further three days and so on.



On day 3, median Cmin fell within the therapeutic range in all study groups. CYP3A5 expressors require significantly higher Tac-OD throughout the follow-up period to achieve a comparable Cmin.



This simplified strategy does not hamper treatment efficacy.
Department of Surgery, Surgery & Abdominal Transplantation Division, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Martine
M
De Meyer
Department of Clinical Chemistry, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.|Louvain Centre for Toxicology & Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium.
Vincent
V
Haufroid
Department of Nephrology, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Nada
N
Kanaan
Department of Surgery, Surgery & Abdominal Transplantation Division, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Tom
T
Darius
Department of Surgery, Surgery & Abdominal Transplantation Division, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Antoine
A
Buemi
Department of Surgery, Surgery & Abdominal Transplantation Division, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Luc
L
De Pauw
Department of Surgery, Surgery & Abdominal Transplantation Division, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Djamila Chaïb
DC
Eddour
Department of Clinical Chemistry, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Pierre
P
Wallemacq
Department of Surgery, Surgery & Abdominal Transplantation Division, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Michel
M
Mourad
D000328:Adult; D000368:Aged; D000483:Alleles; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004247:DNA / Q000235:genetics; D003692:Delayed-Action Preparations; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods*; D010865:Pilot Projects; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*
D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D004247:DNA; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
extended release tacrolimus; immunosuppression; kidney transplant; ­pharmacogenomics