Initial Dosage Range of Tacrolimus by Genotyping in Chinese Renal Transplantation
Status:
Completed
Trial end date:
2011-06-01
Target enrollment:
Participant gender:
Summary
Acute rejection (AR) is the main complication after transplantation, which is a severe risk
of chronic rejection and implant devitalization.
Tacrolimus (FK506) is an immunosuppressant used for the prevention of episodes of acute
rejection. Tacrolimus is characterized by a narrow therapeutic index and important
interindividual variations of its pharmacokinetic characteristics.
Tacrolimus is metabolized through the liver by the cytochrome P450 system, the cytochrome
P450 3A5 (CYP 3A5) isoenzyme specifically. Polymorphisms in the CYP 3A5 gene have been
associated with changes in metabolic function of the translated isoenzyme. These
polymorphisms result in metabolism acceleration of tacrolimus as compared to subjects having
the wild type gene, consequently leading to insufficiency of tacrolimus; it is theorized that
this leads to higher risk of acute rejection. Several retrospective studies suggested an
association between a genetic polymorphism of CYP3A5 and the interindividual variations of
tacrolimus blood concentration. In particular, our initial study showed that adult renal
transplant recipients with the CYP3A5*1/*3 and *1/*1 （expressors） genotype require higher,
fixed, starting dose compared with CYP3A5*3/*3 （nonexpressor）to reach the predefined target
exposure early after transplantation.
This prospective study is designed to evaluate whether genetic testing of CYP 3A5 can improve
tacrolimus initiation better than usual care. This study is a prospective, multicentric,
open, parallel , efficacy study. 300 receivers of a renal transplant in 8 centres will be
included.
The genotyping of gene CYP3A5 will be carried out in the 4-7days before renal
transplantation. After transplantation, the patients will be treated by MMF, corticosteroids
and tacrolimus at a dosage adapted to their genotype(0.15mg/kg/d for CYP3A5*1/*1 type and
CYP3A5*1/*3 type，0.08mg/kg/d for CYP3A5*3/*3 type).
The determination of tacrolimus blood concentration will be carried out on Day
3,5,7,14,18,21,28,35,49,63,77,90. The daily amounts of tacrolimus could be modified if
necessary to reach the desired blood concentrations. The total duration of the study for a
patient is 3 months after transplantation.
The objective of this study is to determine the initial dosage of tacrolimus in Chinese renal
transplantation patients by genotyping of the cytochrome P450 3A5
Phase:
Phase 4
Details
Lead Sponsor:
The Second Artillery General Hospital
Collaborators:
Air Force General Hospital of the PLA Capital Medical University Health Department of General Logistics Pharmacology Research Institute Shanghai Changzheng Hospital