Genetic factors for individual administration of immunosuppressants in organ transplantation.
BACKGROUND
The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug efflux pump P-glycoprotein (P-gp) are two potential factors in the processes of metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these two enzymes. This review was undertaken to assess the role of single nuclear polymorphisms (SNPs) of these two enzymes in the individual administration of immunosuppressive drugs.


METHODS
An English-language literature search was made using MEDLINE for articles on CYP3A and P-gp in organ transplantation.


RESULTS
The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conflicting results were obtained by some authors.


CONCLUSIONS
More studies should be conducted to elucidate further the pharmacogenetics of immunosuppressive drugs in organ transplantation, a deep understanding of which would provide an important step toward drug regimen individualization in the posttransplant therapy.
Yu
Song-Feng
SF
Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Wu
Li-Hua
LH
Zheng
Shu-Sen
SS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016377:Organ Transplantation; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D051544:Cytochrome P-450 CYP3A