ArticleBritish journal of clinical pharmacology2021
Population pharmacokinetics and genetics of oral meltdose tacrolimus (Envarsus) in stable adult liver transplant recipients.
Article in British journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Relevance-Based Score for MIPD Model Selection: Systematic Review and External Evaluation of popPK Tacrolimus Models in Adult Transplant Recipients.CPT: pharmacometrics & systems pharmacology · 2026Pooled it
- A Review of Population Pharmacokinetic Models and Dosing Algorithms Assessing the Influence of CYP3A5 Genotype and Other Clinical Covariates on Tacrolimus Pharmacokinetics.Clinical pharmacokinetics · 2026Review
- Graft bile analysis for predicting post-transplant outcomes: A literature review and a protocol for a novel biomarker.World journal of gastrointestinal surgery · 2026Review
- Combined donor-recipient CYP3A functional allele count as an independent predictor of tacrolimus pharmacokinetics after liver transplantation.Frontiers in pharmacology · 2026Article
- Leveraging machine learning in limited sampling strategies for efficient estimation of the area under the curve in pharmacokinetic analysis: a review.European journal of clinical pharmacology · 2025Review
- External validation of population pharmacokinetic models of tacrolimus in Thai adult liver transplant recipients.European journal of clinical pharmacology · 2024Article
- Article
- Meltdose Tacrolimus Population Pharmacokinetics and Limited Sampling Strategy Evaluation in Elderly Kidney Transplant Recipients.Pharmaceutics · 2023Article
- Article
- Tacrolimus pharmacokinetics in pediatric nephrotic syndrome: A combination of population pharmacokinetic modelling and machine learning approaches to improve individual prediction.Frontiers in pharmacology · 2022Article
- Population pharmacokinetics and genetics of oral meltdose tacrolimus (Envarsus) in stable adult liver transplant recipients.British journal of clinical pharmacology · 2021Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsMeltdose tacrolimus (Envarsus) is marketed as a formulation with a more consistent exposure. Due to the narrow therapeutic window, therapeutic drug monitoring is essential to maintain adequate exposure. The primary objective of this study was to develop a population pharmacokinetic (PK) model of Envarsus among liver transplant patients and select a limited sampling strategy (LSS) for AUC estimation. The secondary objective was to investigate potential covariates including CYP3A/IL genotype suitable for initial dose optimization when converting to Envarsus.
methodsAdult liver transplant patients were converted from prolonged release tacrolimus (Advagraf) to Envarsus and blood samples were obtained using whole blood and dried blood spot sampling. Subsequently the population PK parameters were estimated using nonlinear-mixed effect modelling. Demographic factors, and recipient and donor CYP3A4, CYP3A5, IL-6, -10 and -18 genotype were tested as potential covariates to explain interindividual variability.
resultsFifty-five patients were included. A 2-compartment model with delayed absorption was the most suitable to describe population PK parameters. The population PK parameters were as follows: clearance, 3.27 L/h; intercompartmental clearance, 9.6 L/h; volume of distribution of compartments 1 and 2, 95 and 500 L, respectively. No covariates were found to significantly decrease interindividual variability. The best 3-point LSS was t = 0,4,8 with a median bias of 1.8% (-12.5-12.5).
conclusionsThe LSS can be used to adequately predict the AUC. No clinically relevant covariates known to influence the PK of Envarsus, including CYP3A status, were identified and therefore do not seem useful for initial dose optimization.
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