ArticlePloS one2020
Pharmacogenetic-Whole blood and intracellular pharmacokinetic-Pharmacodynamic (PG-PK2-PD) relationship of tacrolimus in liver transplant recipients.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01388387 (Impact of Donor and Recipient CYP3A5 Genetic Polymorphism on Tacrolimus Exposure in Patients With Hepatic Transplant), which is not on this map. Cited by 16 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Impact of Donor and Recipient CYP3A5 Genetic Polymorphism on Tacrolimus Exposure in Patients With Hepatic Transplant
Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- A Novel Laboratory-Developed Test Using Multiplex qPCR to Further Personalize Tacrolimus Dosing.International journal of molecular sciences · 2026Article
- Graft bile analysis for predicting post-transplant outcomes: A literature review and a protocol for a novel biomarker.World journal of gastrointestinal surgery · 2026Review
- Robust UPLC-MS/MS Method With Acetonitrile for Precise Intracellular Quantification of Tacrolimus in PBMCs: A Step Toward Clinical Integration.Clinical and translational science · 2025Article
- Improving prediction of tacrolimus concentration using a combination of population pharmacokinetic modeling and machine learning in chinese renal transplant recipients.Frontiers in pharmacology · 2024Article
- Importance of Pharmacogenetics and Drug-Drug Interactions in a Kidney Transplanted Patient.Life (Basel, Switzerland) · 2023Article
- The Effect of Intracellular Tacrolimus Exposure on Calcineurin Inhibition in Immediate- and Extended-Release Tacrolimus Formulations.Pharmaceutics · 2023Article
- Adaptation of a population pharmacokinetic model to inform tacrolimus therapy in heart transplant recipients.British journal of clinical pharmacology · 2023Article
- Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics.Pharmaceutics · 2022Review
- A Population Pharmacokinetic Model of Whole-Blood and Intracellular Tacrolimus in Kidney Transplant Recipients.European journal of drug metabolism and pharmacokinetics · 2022Article
- Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up.Pharmaceutics · 2022Article
- Monitoring the tacrolimus concentration in peripheral blood mononuclear cells of kidney transplant recipients.British journal of clinical pharmacology · 2021Article
- Influence of the Circadian Timing System on Tacrolimus Pharmacokinetics and Pharmacodynamics After Kidney Transplantation.Frontiers in pharmacology · 2021Article
- Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients.Frontiers in pharmacology · 2021Article
- Monitoring Intra-cellular Tacrolimus Concentrations in Solid Organ Transplantation: Use of Peripheral Blood Mononuclear Cells and Graft Biopsy Tissue.Frontiers in pharmacology · 2021Review
- Influential Factors and Efficacy Analysis of Tacrolimus Concentration After Allogeneic Hematopoietic Stem Cell Transplantation in Children with β-Thalassemia Major.Pharmacogenomics and personalized medicine · 2021Article
- Maintenance Immunosuppression in Solid Organ Transplantation: Integrating Novel Pharmacodynamic Biomarkers to Inform Calcineurin Inhibitor Dose Selection.Clinical pharmacokinetics · 2020Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tacrolimus (TAC) is the cornerstone of immunosuppressive therapy in liver transplantation. This study aimed at elucidating the interplay between pharmacogenetic determinants of TAC whole blood and intracellular exposures as well as the pharmacokinetic-pharmacodynamic relationship of TAC in both compartments. Complete pharmacokinetic profiles (Predose, and 20 min, 40 min, 1h, 2h, 3h, 4h, 6h, 8h, 12h post drug intake) of twice daily TAC in whole blood and peripheral blood mononuclear cells (PBMC) were collected in 32 liver transplanted patients in the first ten days post transplantation. A non-parametric population pharmacokinetic model was applied to explore TAC pharmacokinetics in blood and PBMC. Concurrently, calcineurin activity was measured in PBMC. Influence of donor and recipient genetic polymorphisms of ABCB1, CYP3A4 and CYP3A5 on TAC exposure was assessed. Recipient ABCB1 polymorphisms 1199G>A could influence TAC whole blood and intracellular exposure (p<0.05). No association was found between CYP3A4 or CYP3A5 genotypes and TAC whole blood or intracellular concentrations. Finally, intra-PBMC calcineurin activity appeared incompletely inhibited by TAC and less than 50% of patients were expected to achieve intracellular IC50 concentration (100 pg/millions of cells) at therapeutic whole blood concentration (i.e.: 4-10 ng/mL). Together, these data suggest that personalized medicine regarding TAC therapy might be optimized by ABCB1 pharmacogenetic biomarkers and by monitoring intracellular concentration whereas the relationship between intracellular TAC exposure and pharmacodynamics biomarkers more specific than calcineurin activity should be further investigated.
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