Genetic polymorphisms of CYP3A5 genes and concentration of the cyclosporine and tacrolimus.
OBJECTIVE
CYP3A is the major enzyme responsible for metabolism of the calcineurin inhibitors cyclosporine (CsA) and tacrolimus. Our objective was to determine the relationship between genetic polymorphisms of CYP3A5 with respect to interindividual variability in CsA and tacrolimus pharmacokinetics.


METHODS
Kidney transplant recipients receiving CsA (n = 137) or tacrolimus (n = 30) were genotyped for CYP3A5*3 and *6 by a PCR/RFLP method. The patients were grouped according to the CYP3A5 genotype. Dose-adjusted trough levels were correlated with the corresponding genotype.


RESULTS
At 3, 6, and 12 months, the tacrolimus dose-adjusted trough levels (dose-adjusted C0) showed a statistically significant difference between the group of CYP3A5*3/*3 (n = 19) and the group of CYP3A5*1 allele carriers. The former was higher than the latter. The CsA dose-adjusted C0 and the actual C0 did not display a significant relation (P < .05) between the group of CYP3A5*3/*3 and the group of CYP3A5*1 allele carriers.


CONCLUSIONS
Patients with the CYP3A5*3/*3 genotype require less tacrolimus to reach target concentrations compared to those with the CYP3A5*1 allele.
Zhao
Y
Y
The First Hospital of Tsinghua University, Beijing, China.
Song
M
M
Guan
D
D
Bi
S
S
Meng
J
J
Li
Q
Q
Wang
W
W
D001483:Base Sequence; D002681:China; D016572:Cyclosporine / Q000627:therapeutic use*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016559:Tacrolimus / Q000627:therapeutic use*
D017931:DNA Primers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus