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  • Title: Genotype-guided tacrolimus dosing in African-American kidney transplant recipients.
    Author: Sanghavi K, Brundage RC, Miller MB, Schladt DP, Israni AK, Guan W, Oetting WS, Mannon RB, Remmel RP, Matas AJ, Jacobson PA.
    Journal: Pharmacogenomics J; 2017 Jan; 17(1):61-68. PubMed ID: 26667830.
    Abstract:
    Tacrolimus is dependent on CYP3A5 enzyme for metabolism. Expression of the CYP3A5 enzyme is controlled by several alleles including CYP3A5*1, CYP3A5*3, CYP3A5*6 and CYP3A5*7. African Americans (AAs) have on average higher tacrolimus dose requirements than Caucasians; however, some have requirements similar to Caucasians. Studies in AAs have primarily evaluated the CYP3A5*3 variant; however, there are other common nonfunctional variants in AAs (CYP3A5*6 and CYP3A5*7) that do not occur in Caucasians. These variants are associated with lower dose requirements and may explain why some AAs are metabolically similar to Caucasians. We created a tacrolimus clearance model in 354 AAs using a development and validation cohort. Time after transplant, steroid and antiviral use, age and CYP3A5*1, *3, *6 and *7 alleles were significant toward clearance. This study is the first to develop an AA-specific genotype-guided tacrolimus dosing model to personalize therapy.
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