ArticleBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation2016
Influence of Absorption, Distribution, Metabolism, and Excretion Genomic Variants on Tacrolimus/Sirolimus Blood Levels and Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation.
Article in Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- Polymorphisms inFrontiers in pharmacology · 2025Pooled it
- Effects ofCurrent pharmaceutical design · 2024Pooled it
- Meta-Analysis of Genome-Wide Association and Gene Expression Studies Implicates Donor T Cell Function and Cytokine Pathways in Acute GvHD.Frontiers in immunology · 2020Pooled it
- Evaluation of the performance of a prior tacrolimus population pharmacokinetic kidney transplant model among adult allogeneic hematopoietic stem cell transplant patients.Clinical and translational science · 2021Trial
- Pharmacokinetic Model of Drug Interaction of Tacrolimus with Combined Administration of CYP3A4 Inhibitors Voriconazole and Clarithromycin After Bone Marrow Transplantation.European journal of drug metabolism and pharmacokinetics · 2024Article
- Effects ofPharmaceuticals (Basel, Switzerland) · 2024Article
- Three Layers of Personalized Medicine in the Use of Sirolimus and Its Derivatives for the Treatment of Cancer.Journal of personalized medicine · 2023Review
- Precision sirolimus dosing in children: The potential for model-informed dosing and novel drug monitoring.Frontiers in pharmacology · 2023Review
- Article
- Tacrolimus initial steady state level in post-transplant cyclophosphamide-based GvHD prophylaxis regimens.Bone marrow transplantation · 2022Article
- [The effect of CYP3A5 gene polymorphism on tacrolimus concentration and adverse events in patients undergoing allogeneic hematopoietic stem cell transplantation].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Article
- Intrapatient variability in concentration/dose ratio of tacrolimus predicts transplant-associated thrombotic microangiopathy.International journal of hematology · 2021Article
- Association Between Neighborhood-level Socioeconomic Deprivation and the Medication Level Variability Index for Children Following Liver Transplantation.Transplantation · 2020Observational
- Kidney podocyte-associated gene polymorphisms affect tacrolimus concentration in pediatric patients with refractory nephrotic syndrome.The pharmacogenomics journal · 2020Article
- Influence of Germline Genetics on Tacrolimus Pharmacokinetics and Pharmacodynamics in Allogeneic Hematopoietic Stem Cell Transplant Patients.International journal of molecular sciences · 2020Article
- Impact ofInternational journal of molecular sciences · 2019Article
- Genotypes associated with tacrolimus pharmacokinetics impact clinical outcomes in lung transplant recipients.Clinical transplantation · 2018Article
- Genome-wide association study identifies the common variants in CYP3A4 and CYP3A5 responsible for variation in tacrolimus trough concentration in Caucasian kidney transplant recipients.The pharmacogenomics journal · 2018Article
- Association analysis between SUFU polymorphism rs17114808 and acute graft versus host disease after hematopoietic stem cell transplantation.Bone marrow transplantation · 2018Article
- Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients.Pharmacogenomics · 2018Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Allelic variants of genes implicated in drug absorption, distribution, metabolism, and excretion (ADME) determine the pharmacokinetic variability of many medications and are increasingly recognized as important factors determining the success or failure of medical treatments. Both tacrolimus and sirolimus have narrow therapeutic ranges maintained by therapeutic drug monitoring (TDM). Using an ADME panel that covers >99% of the PharmaADME working group core list (188 single nucleotide polymorphism [SNP] and 12 copy number variant [CNV] assays in 36 pharmacogenetically relevant genes), we studied 177 patients who underwent allogeneic hematopoietic cell transplantation (HCT) using tacrolimus/sirolimus-based graft-versus-host disease (GVHD) prophylaxis. We tested for possible associations between ADME variants and tacrolimus/sirolimus drug levels, concentration/dose (C/D) ratio, and clinical endpoints, including acute GVHD. A total of 62 SNP and 6 CNV assays were evaluable after removing the variants, which were homozygous in (nearly) all samples. For sirolimus, rs2032582 (ABCB1) T-carriers versus non-T-carriers were associated with higher blood levels (P = .01), with similar results for C/D ratio. Generalized estimating equation analysis supported these findings. For tacrolimus, rs776746 CYP3A5*3/*3 and CYP3A5*3/*1 were associated with higher blood levels than CYP3A5*1/*1 (P = .002). By multivariable analysis, rs776746 CYP3A5*3/*3 and CYP3A5*3/*1 were independently associated with decreased acute GVHD compared with CYP3A5*1/*1, after adjustment for conditioning, donor type, race/ethnicity, and age. We demonstrated association of specific ADME genetic polymorphisms with blood levels of tacrolimus/sirolimus, and incidence of acute GVHD after HCT, in spite of TDM and dose adjustment. A larger ongoing study will determine whether these associations have clinical utility beyond TDM.
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