ArticleEuropean journal of drug metabolism and pharmacokinetics2020
High Variability of Whole-Blood Tacrolimus Pharmacokinetics Early After Thoracic Organ Transplantation.
Article in European journal of drug metabolism and pharmacokinetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Model-Informed Precision Dosing of Tacrolimus: A Systematic Review of Population Pharmacokinetic Models and a Benchmark Study of Software Tools.Clinical pharmacokinetics · 2024Pooled it
- Population Pharmacokinetic Models of Tacrolimus in Adult Transplant Recipients: A Systematic Review.Clinical pharmacokinetics · 2020Pooled it
- Discordance between trough concentration and tacrolimus exposure on the day of kidney transplantation: a prospective pharmacokinetic study.Frontiers in pharmacology · 2026Article
- Towards Personalized Tacrolimus Dosing Using an Algorithm-Driven Prediction Pipeline for Kidney Transplant.Drug design, development and therapy · 2026Article
- Population pharmacokinetic characteristics of tacrolimus in Chinese lung transplant recipients and optimisation of dosing regimen during the early post-transplantation phase.European journal of clinical pharmacology · 2025Article
- Intramuscular Tacrolimus Pharmacokinetics in a Pediatric Porcine Model for Partial Heart Transplantation.Transplantation proceedings · 2025Article
- The tacrolimus concentration-to-dose ratio is associated with kidney function in heart transplant recipients.British journal of clinical pharmacology · 2025Article
- Tacrolimus Pharmacotherapy: Infectious Complications and Toxicity in Organ Transplant Recipients; An Updated Review.Current drug research reviews · 2025Review
- Development and validation of a population pharmacokinetic model to guide perioperative tacrolimus dosing after lung transplantation.JHLT open · 2024Article
- Tacrolimus Variability and Clinical Outcomes in the Early Post-lung Transplantation Period: Oral Versus Continuous Intravenous Administration.Clinical pharmacokinetics · 2024Article
- Pharmacokinetic Evaluation of Tacrolimus in Chinese Adult Patients during the Early Stages Post-Lung Transplantation.Journal of personalized medicine · 2023Article
- Adaptation of a population pharmacokinetic model to inform tacrolimus therapy in heart transplant recipients.British journal of clinical pharmacology · 2023Article
- Tacrolimus-why pharmacokinetics matter in the clinic.Frontiers in transplantation · 2023Review
- Clinical Implications of Tacrolimus Time in Therapeutic Range and Intrapatient Variability in Urban Renal Transplant Recipients Undergoing Early Corticosteroid Withdrawal.Transplantation direct · 2021Article
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
BACKGROUND AND
objectiveOral tacrolimus is initiated perioperatively in heart and lung transplantation patients. There have been few studies on oral tacrolimus pharmacokinetics early post-transplantation, even though tacrolimus-related toxicity may occur early, potentially leading to morbidity and mortality. Therefore, we aimed to study the pharmacokinetics of oral tacrolimus in thoracic organ recipients during the first days after transplantation.
methodsWe conducted a pharmacokinetic study in 30 thoracic organ transplants at intensive care at the University Medical Center Utrecht in the first week post-transplantation. Twelve-hour whole-blood tacrolimus profiles were examined using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) and analysed via population pharmacokinetic modelling.
resultsThe concentration-time profiles showed high variability. Concentrations at 12 h were outside the target range in 69% of the cases. A two-compartment model with mixed first-order and zero-order absorption adequately described tacrolimus concentrations. The typical value of the apparent clearance was 19.6 L/h (95% CI 16.2-22.9), and the apparent distribution volumes of central and peripheral compartments, V1 and V2, were 231 L (95% CI 199-267) and 521 L (95% CI 441-634), respectively. Inter-occasion (dose-to-dose) variability far exceeded the interindividual variability (IIV), with an estimated variability in relative bioavailability of 55% (95% CI 48.5-64.4).
conclusionsThe high variability of tacrolimus pharmacokinetics early after thoracic organ transplantation is largely due to excessive variability in bioavailability, making individualised dosing based on measured concentrations futile. To bypass this bioavailability issue, we suggest administering tacrolimus intravenously and aiming below the upper therapeutic range early post-transplantation. Clinical Trial Registraion: NTR 3912/EudraCT 2012-001909-24.
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