CYP3A5 Polymorphism in Mexican Renal Transplant Recipients and its Association with Tacrolimus Dosing

García-Roca, Pilar; Medeiros-Domingo, Mara; Reyes, Herlinda; Rodríguez-Espino, Benjamín Antonio; Alberú, Josefina; Ortíz, Lourdes; Vásquez-Perdomo, Mayela; Elizondo, Guillermo; Morales‐Buenrostro, Luis E.; Urrea, Eduardo Mancilla; Castañeda‐Hernández, Gilberto

doi:10.1016/j.arcmed.2012.05.005

Cited by 37 publications

(32 citation statements)

References 31 publications

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“…CYP3A4/5 is predominantly responsible for the conversion of TAM to N-DMT. A SNP in CYP3A5 (*3, 6986 G > A, rs776746) with decreased enzyme activity is prevalent (52 %) in Hispanics [43]. Additionally, TAM undergoes N-oxidation catalyzed by FMO to form tamoxifen-N-oxide, which is converted back to TAM by CYP450's, such as CYP1A6 and CYP1A1 [44].…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in Hispanics and non-Hispanic whites with breast cancer

Rangel

Taraba

Frei

et al. 2014

Breast Cancer Res Treat

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Ethnic differences in patient genetics and breast cancer (BC) biology contribute to ethnic disparities in cancer presentation and patient outcome. We prospectively evaluated SNPs within phase I and phase II tamoxifen (TAM) metabolizing enzymes, and the estrogen receptor gene (ESR1), aiming to identify potential pharmacogenomic ethnicity patterns in an ER-positive BC cohort constituted of Hispanic and Non-Hispanic White (NHW) women in South Texas. Plasma concentrations of TAM/metabolites were measured using HPLC. CYP2C9, CYP2D6 and SULT1A1 genotypes were determined by DNA sequencing/Pyrosequencing technology. ESR1 PvuII and XbaI SNPs were genotyped using Applied Biosystems Taqman® Allelic Discrimination Assay. Hispanics had higher levels of TAM, 4-hydroxytamoxifen, and endoxifen than NHWs. There was a higher prevalence of CYP2D6 EM within Hispanics than NHWs, which corresponded to higher endoxifen levels, but no differences were verified with regard to CYP2C9 and SULT1A1. We found a higher incidence of the wild type forms of the ESR1 in Hispanics than NHWs. The performance status, the disease stage at diagnosis, and the use of aromatase inhibitors might have overcome the overall favorable pharmacogenomics profile of Hispanics when compared to NHWs in relation to TAM therapy responsiveness. Our data strongly point to ethnical peculiarities related to pharmacogenomics and demographic features of TAM treated Hispanics and NHWs. In the era of pharmacogenomics and its ultimate goal of individualized, efficacious and safe therapy, cancer studies focused on the Hispanic population are warranted because this is the fastest growing major demographic group, and an understudied segment in the U.S.

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Section: Discussionmentioning

confidence: 99%

Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in Hispanics and non-Hispanic whites with breast cancer

Rangel

Taraba

Frei

et al. 2014

Breast Cancer Res Treat

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“…The quantification was performed in whole blood, using CMIA in an ARCHITECT i1000SR system (Abbott‐Laboratories). The assay was validated according to the manufacturer's and the quality standards of the Pharmacology Laboratory of Hospital Infantil de Mexico Federico Gomez …”

Section: Methodsmentioning

confidence: 99%

Limited sampling strategy to predict the area under the curve of tacrolimus in Mexican renal transplant pediatric patients receiving Prograf^® or non‐innovator formulations

Medina-Aymerich

González-Ramírez

García-Roca

et al. 2019

Pediatric Transplantation

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TDM of tacrolimus is usually performed with trough levels (C0h). However, in pediatric patients, C0h may not be an adequate marker. The AUC is considered a more suitable indicator of drug exposure. As several blood samples are needed for the estimation of AUC, and LSS for predicting tacrolimus AUC and optimizing the dose adjustment have been proposed. Moreover, in emerging countries such as Mexico, non‐innovator formulations, which bioequivalence has not been demonstrated, are frequently used. Hence, the aim of this study was to develop and validate a LSS to predict the tacrolimus AUC0‐12h in Mexican pediatric kidney transplant recipients who received either Prograf® or non‐innovator tacrolimus formulations. A total of 56 pharmacokinetic profiles were randomized into two groups: model development (n = 28) and model validation (n = 28). The limited sampling equations were obtained after a stepwise multiple regression using AUC as the dependent variable and tacrolimus blood concentrations, quantified by CMIA, at different time points as the independent variables. The final equation included observed concentrations at 1 hour (C1h) and 4 hours (C4h) after dose administration. The predictive performance of the model was adequate in terms of both, bias and precision. Results strongly suggest that the clinical use of this LSS could provide an ethical, cost‐, and time‐effective method in the TDM of tacrolimus in pediatric patients with kidney transplant. The model proved to be adequate with either Prograf® or non‐innovator tacrolimus formulations of dubious bioequivalence.

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“…The effect of CYP3A5 genotype on dose‐corrected tacrolimus concentration in pediatric populations has been studied in several clinical settings, including heart and liver transplantation, but most extensively after kidney transplantation . Unfortunately, available data vary in terms of study duration after transplant and inclusion of additional factors that impact the dose‐exposure relationship.…”

Section: Drug: Tacrolimusmentioning

confidence: 99%

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

Birdwell

Decker

Barbarino

et al. 2015

Clin Pharma and Therapeutics

540

519

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Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared to those who are CYP3A5 non-expressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).

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CYP3A5 Polymorphism in Mexican Renal Transplant Recipients and its Association with Tacrolimus Dosing

Cited by 37 publications

References 31 publications

Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in Hispanics and non-Hispanic whites with breast cancer

Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in Hispanics and non-Hispanic whites with breast cancer

Limited sampling strategy to predict the area under the curve of tacrolimus in Mexican renal transplant pediatric patients receiving Prograf^® or non‐innovator formulations

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

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CYP3A5 Polymorphism in Mexican Renal Transplant Recipients and its Association with Tacrolimus Dosing

Cited by 37 publications

References 31 publications

Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in Hispanics and non-Hispanic whites with breast cancer

Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in Hispanics and non-Hispanic whites with breast cancer

Limited sampling strategy to predict the area under the curve of tacrolimus in Mexican renal transplant pediatric patients receiving Prograf® or non‐innovator formulations

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

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Product

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Limited sampling strategy to predict the area under the curve of tacrolimus in Mexican renal transplant pediatric patients receiving Prograf^® or non‐innovator formulations