ArticleDrugs in R&D2017
The Pharmacogenetics of Tacrolimus in Corticosteroid-Sparse Pediatric and Adult Kidney Transplant Recipients.
Article in Drugs in R&D, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies.BMC nephrology · 2024Pooled it
- Effects ofFrontiers in pharmacology · 2023Pooled it
- Introduction to Pharmacogenomics: Role of the Histocompatibility and Immunogenetics Laboratory in Personalised Medicine-Current Status and Future Prospects.International journal of immunogenetics · 2026Review
- Tacrolimus pharmacokinetics are influenced by CYP3A5, age, and concomitant fluconazole in pediatric kidney transplant patients.Clinical and translational science · 2023Article
- Association of P450 Oxidoreductase Gene Polymorphism with Tacrolimus Pharmacokinetics in Renal Transplant Recipients: A Systematic Review and Meta-Analysis.Pharmaceutics · 2022Review
- 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
- Review
- CYP3A5 and CYP3A7 genetic polymorphisms affect tacrolimus concentration in pediatric patients with nephrotic range proteinuria.European journal of clinical pharmacology · 2019Article
- Tacrolimus troughs and genetic determinants of metabolism in kidney transplant recipients: A comparison of four ancestry groups.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Observational
- Biomarkers and Pharmacogenomics in Kidney Transplantation.Molecular diagnosis & therapy · 2018Review
- Indian National Association for the Study of the Liver-Federation of Obstetric and Gynaecological Societies of India Position Statement on Management of Liver Diseases in Pregnancy.Journal of clinical and experimental hepatologyReview
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTacrolimus is a calcineurin inhibitor used as an immunosuppressant drug in solid organ transplantation, and is mainly metabolized by cytochrome P450 (CYP) 3A4 and CYP3A5. Studies have shown an association between the CYP3A5 genotype and tacrolimus dose-adjusted trough concentrations. Variants in the genes PPARA, POR and CYP3A4 have recently been shown to influence tacrolimus metabolism. Furthermore, pharmacokinetic interaction between corticosteroid treatment and tacrolimus has been shown. In the present study, we investigated a potential association between CYP3A5*3, PPARA c.209-1003G>A, POR*28 and CYP3A4*22 and dose-adjusted tacrolimus trough concentrations in a primarily corticosteroid-free (>85%) population of Danish pediatric and adult kidney transplant recipients.
methodsSeventy-two patients receiving treatment with oral tacrolimus were genotyped using real-time polymerase chain reaction and Primer-Probe Detection. Tacrolimus trough concentrations, corresponding doses and covariates were retrospectively collected from the patients' medical charts.
resultsIt was confirmed that CYP3A5*1 wild-type carriers had lower median dose-adjusted tacrolimus trough concentrations compared with noncarriers. Adults had 56 and 77% lower trough concentrations at 6 weeks (p = 0.0003) and 1 year, respectively (p < 0.0017), and, similarly, children had 65 and 39% lower median concentrations, with p values of 0.006 and 0.011, respectively. No association was found for PPARA c.209-1003G>A, POR*28, or CYP3A4*22. An association between the PPARA c.209-1003G>A genotype and an increased number of infections with cytomegalovirus (CMV) within the first year was identified (p < 0.05). Only 29% of trough concentrations measured between 2 and 12 weeks post-transplantation were on target.
conclusionThis study shows that the known association of the CYP3A5 genotype with tacrolimus dose-adjusted trough concentrations has the same impact in a corticosteroid-sparse population. The association between PPARA variance and infections with CMV will need further investigation.
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