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  • Title: Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients.
    Author: Thervet E, Anglicheau D, King B, Schlageter MH, Cassinat B, Beaune P, Legendre C, Daly AK.
    Journal: Transplantation; 2003 Oct 27; 76(8):1233-5. PubMed ID: 14578760.
    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. METHODS: CYP3A5 genotype was evaluated in 80 renal transplant recipients and correlated with the daily tacrolimus dose and concentration-to-dose ratio. 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. 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.
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