ArticleEuropean journal of clinical pharmacology2012
The interactions of age, sex, body mass index, genetics, and steroid weight-based doses on tacrolimus dosing requirement after adult kidney transplantation.
Article in European journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
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.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- CYP3A5 gene polymorphisms and their impact on dosage and trough concentration of tacrolimus among kidney transplant patients: a systematic review and meta-analysis.The pharmacogenomics journal · 2020Pooled it
- Risk factors for calcineurin inhibitor nephrotoxicity after renal transplantation: a systematic review and meta-analysis.Drug design, development and therapy · 2018Pooled it
- Prolonged-Release Once-Daily Formulation of Tacrolimus Versus Standard-of-Care Tacrolimus inTransplant international : official journal of the European Society for Organ Transplantation · 2022Trial
- Pharmacokinetics of Prolonged-Release Once-Daily Formulations of Tacrolimus in De Novo Kidney Transplant Recipients: A Randomized, Parallel-Group, Open-Label, Multicenter Study.Advances in therapy · 2019Trial
- Lack of a significant pharmacokinetic interaction between maraviroc and tacrolimus in allogeneic HSCT recipients.The Journal of antimicrobial chemotherapy · 2015Trial
- Multidrug resistance-associated protein 2 (MRP2/ABCC2) haplotypes significantly affect the pharmacokinetics of tacrolimus in kidney transplant recipients.Clinical pharmacokinetics · 2013Trial
- Concentration-to-Dose Ratio Differences Between Once-Daily Tacrolimus Formulations: A Five-Year Real-World Pharmacokinetic Study in Kidney Transplantation.European journal of drug metabolism and pharmacokinetics · 2026Article
- Envarsus Versus Advagraf in De Novo Kidney Transplant Recipients: A Comparative Pharmacokinetic Study.Life (Basel, Switzerland) · 2026Article
- Integrating pharmacogenetic and clinical factors to predict the C0/D/W-based tacrolimus phenotype in kidney transplantation.Frontiers in pharmacology · 2026Article
- Clinical Factors Influencing Tacrolimus Metabolism and Blood Level Early After Kidney Transplantation-A Comparison of Three Different Tacrolimus Formulations.Journal of clinical medicine · 2025Article
- Associations between the gut microbiota and the metabolism rate of tacrolimus in kidney transplant recipients during the early posttransplant period.Archives of pharmacal research · 2025Observational
- Optimization of the Tacrolimus Concentration-to-Dose Ratio Cut-Off Value to Define Metabolism Groups.Journal of clinical medicine · 2025Article
- Clinical-oriented tacrolimus dosing algorithms in kidney transplant based on genetic algorithm and deep forest.Frontiers in pharmacology · 2025Article
- Characterizing the Use of Prolonged-Release Once-Daily Tacrolimus (LCPT) across Canada.The Canadian journal of hospital pharmacy · 2025Article
- Single Nucleotide Polymorphisms of CYP3A4 and CYP3A5 in Romanian Kidney Transplant Recipients: Effect on Tacrolimus Pharmacokinetics in a Single-Center Experience.Journal of clinical medicine · 2024Article
- Tacrolimus Concentration/Dose Ratio: A Tool for Guiding Tacrolimus Dosage Post-renal Transplantation.Cureus · 2024Article
- Identification of Drugs Acting as Perpetrators in Common Drug Interactions in a Cohort of Geriatric Patients from Southern Italy and Analysis of the Gene Polymorphisms That Affect Their Interacting Potential.Geriatrics (Basel, Switzerland) · 2023Article
- Article
- Intestinal Permeability in Patients Early after Kidney Transplantation Treated with Two Different Formulations of Once-Daily Tacrolimus.International journal of molecular sciences · 2023Article
- Adrenal insufficiency is common amongst kidney transplant recipients receiving maintenance prednisolone and can be predicted using morning cortisol.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe aim of this study was to evaluate the effect of different clinical covariates on tacrolimus dose requirements in adult kidney transplant patients with a specific focus on drug interactions. PATIENTS: Tacrolimus dosing requirement, normalized by drug levels and expressed as the concentration/dose (C/D) ratio as a surrogate index of tacrolimus bioavailability, was employed to identify four categories of tacrolimus dosing requirement, namely, very high, high, small, and very-small, in very fast, fast, slow, and very slow metabolizers, respectively. Steroid weight-based doses were analyzed instead of fixed doses, and genetic analysis of cytochrome P450 (CYP) 3A5*1/*3 and multi-drug resistance 1 (MDR1) C3435T and C1236T polymorphisms were performed
resultsMultivariate analysis on 450 adult transplant patients identified six risk factors for being slow metabolizers and therefore requiring small tacrolimus doses: male sex (OR 1.615, p = 0.020); age >60 years (OR 2.456, p = 0.0005); body mass index ≥ 25 (OR 1.546, p = 0.046), hepatitis C virus positivity (OR 2.800, p = 0.0004); low steroid dose <0.06 mg/kg (OR 3.101, p < 0.0001). Patients with a small tacrolimus requirement were at increased risk for multiple infections (OR 1.533, p = 0.0008) and higher systolic blood pressure (OR 1.385, p = 0.022) and showed a significant association with the CYP3A5*3/*3 genotype adjusted by MDR1 polymorphisms C3435T and C1236T (OR 8.104, p = 0.0001).
conclusionsOur results demonstrate the importance of the interaction among genetic and clinical factors in conditioning tacrolimus disposition, with corticosteroid weight-based dose being the only modifiable risk factor for tacrolimus requirement. As the tacrolimus dosing requirement increases with increasing tacrolimus clearance through concomitant steroid use, undesirable changes in tacrolimus levels may occur when steroid doses are tapered, predominantly in slow metabolizers. This often neglected drug interaction has to be monitored to optimize tacrolimus exposure in kidney transplant patients.
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