ArticleBritish journal of clinical pharmacology2014
Relationship of CYP3A5 genotype and ABCB1 diplotype to tacrolimus disposition in Brazilian kidney transplant patients.
Article in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Impact of cytochrome P450 2C19 polymorphisms on the pharmacokinetics of tacrolimus when coadministered with voriconazole.Journal of clinical pharmacology · 2016Trial
- Non-HLA Genetics and Application to Living Donor Candidates.Current transplantation reports · 2025Article
- Impact of CYP3A5 1* and 3* single nucleotide variants on tacrolimus pharmacokinetics and graft rejection risk in pediatric kidney transplant patients.Frontiers in pharmacology · 2025Article
- Impact ofFrontiers in pharmacology · 2025Article
- Tacrolimus Dose Requirement inTransplant international : official journal of the European Society for Organ Transplantation · 2024Article
- An Improved Technique for Genotyping theMethods and protocols · 2023Article
- Article
- Controversial Interactions of Tacrolimus with Dietary Supplements, Herbs and Food.Pharmaceutics · 2022Review
- Assessment of the Link ofJournal of advanced research · 2021Article
- CYP3A5 and PPARA genetic variants are associated with low trough concentration to dose ratio of tacrolimus in kidney transplant recipients.European journal of clinical pharmacology · 2021Article
- CYP3A5 and UGT1A9 Polymorphisms Influence Immunosuppressive Therapy in Pediatric Kidney Transplant Recipients.Frontiers in pharmacology · 2021Article
- Genetic Polymorphisms Affecting Tacrolimus Metabolism and the Relationship to Post-Transplant Outcomes in Kidney Transplant Recipients.Pharmacogenomics and personalized medicine · 2021Article
- Differential expression of genes related to calcineurin and mTOR signaling and regulatory miRNAs in peripheral blood from kidney recipients under tacrolimus-based therapy.Annals of translational medicine · 2020Article
- Genetics of Childhood Steroid Sensitive Nephrotic Syndrome: An Update.Frontiers in pediatrics · 2019Review
- Effect of CYP3 A4, CYP3 A5 and ABCB1 gene polymorphisms on the clinical efficacy of tacrolimus in the treatment of nephrotic syndrome.BMC pharmacology & toxicology · 2018Article
- Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.Pharmacogenomics · 2018Article
- Artificial neural network model for predicting the bioavailability of tacrolimus in patients with renal transplantation.PloS one · 2018Article
- The Pharmacogenetics of Tacrolimus in Corticosteroid-Sparse Pediatric and Adult Kidney Transplant Recipients.Drugs in R&D · 2017Article
- IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients.Acta pharmacologica Sinica · 2017Article
- Investigation of CYP 3A5 and ABCB1 gene polymorphisms in the long-term following renal transplantation: Effects on tacrolimus exposure and kidney function.Experimental and therapeutic medicine · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTacrolimus (TAC) is one of the most successful immunosuppressive drugs in transplantation. Its pharmacokinetics (PK) and pharmacogenetics (PG) have been extensively studied, with many studies showing the influence of CYP3A5 on TAC metabolism and bioavailability. However, data concerning the functional significance of ABCB1 polymorphisms are uncertain due to inconsistent results. We evaluated the association between ABCB1 diplotypes, CYP3A5 polymorphisms and TAC disposition in a cohort of Brazilian transplant recipients.
methodsIndividuals were genotyped for the CYP3A5*3 allele and ABCB1 polymorphisms (2677G>A/T, 1236C>T, 3435C/T) using a TaqMan® PCR technique. Diplotypes were analyzed for correlation with the TAC dose-normalized ratio (Co : dose).
resultsWe genotyped 108 Brazilian kidney recipients for CYP3A5 (11% CYP3A5*1/*1; 31% CYP3A5*1/*3 and 58% CYP3A5*3/*3) and ABCB1 haplotypes (42% CGC/CGC; 41% GCG/TTT and 17% TTT/TTT). Homozygous subjects for the CYP3A5*3 allele or carriers of the ABCB1 TTT/TTT diplotype showed a higher Co : dose ratio compared with wild type subjects [median (interquartile range) 130.2 (97.5-175.4) vs. 71.3 (45.6-109.0), P < 0.0001 and 151.8 (112.1-205.6) vs. 109.6 (58.1-132.9), P = 0.01, respectively]. When stratified for the CYP3A5*3 group, ABCB1 TTT/TTT individuals showed a higher Co : dose ratio compared with non-TTT/TTT individuals [167.8 (130.4-218.0) vs. 119.4 (100.2-166.3), P = 0.04]. Multivariate linear regression analysis showed that the effects of CYP3A5 polymorphisms and ABCB1 diplotypes remained significant after correction for confounding factors.
conclusionsCYP3A5 is the major enzyme responsible for the marked interindividual variability in TAC PK, but it cannot be considered alone when predicting dose adjustment because ABCB1 diplotypes also affect TAC disposition, showing independent and additive effects on the TAC dose-normalized concentration.
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