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Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients.
- Source :
-
Transplantation [Transplantation] 2003 Oct 27; Vol. 76 (8), pp. 1233-5. - Publication Year :
- 2003
-
Abstract
- Background: Tacrolimus pharmacokinetic characteristics vary greatly among individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes, including CYP3A5. Subjects with the CYP3A5*1/*1 genotype express large amounts of CYP3A5. Heterozygotes (genotype CYP3A5*1/*3) also express the enzyme. We postulated that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations.<br />Methods: CYP3A5 genotype was evaluated in 80 renal transplant recipients and correlated with the daily tacrolimus dose and concentration-to-dose ratio.<br />Results: The frequency of the homozygous CYP3A5*1 genotype (CYP3A5*1/*1) was 5%, and 11% of subjects were heterozygous (CYP3A5*1/*3). The mean doses required to obtain the targeted concentration-to-dose ratio were significantly lower in patients with the CYP3A5*1/*1 genotype.<br />Conclusions: Determination of CYP3A5 genotype is predictive of the dose of tacrolimus in renal transplant recipients and may help to determine the initial daily dose needed by individual patients for adequate immunosuppression without excess nephrotoxicity.
- Subjects :
- Adult
Cytochrome P-450 CYP3A
Dose-Response Relationship, Drug
Female
Gene Frequency
Genotype
Humans
Male
Middle Aged
Osmolar Concentration
Predictive Value of Tests
Cytochrome P-450 Enzyme System genetics
Immunosuppressive Agents administration & dosage
Kidney Transplantation
Polymorphism, Genetic
Tacrolimus administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 0041-1337
- Volume :
- 76
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 14578760
- Full Text :
- https://doi.org/10.1097/01.TP.0000090753.99170.89