ArticleBritish journal of clinical pharmacology2025
Population pharmacokinetics of tacrolimus whole blood and peripheral blood mononuclear cell concentrations in stable kidney-transplanted patients.
Article in British journal of clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- 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
- Impact of aging on the pharmacokinetic profile of everolimus in male mice.BMC pharmacology & toxicology · 2026Article
- Limited Sampling Strategies to Predict Mycophenolic Acid and Tacrolimus Area Under the Concentration-Time Curve in Steroid-Free Kidney Transplant Patients.Basic & clinical pharmacology & toxicology · 2025Article
- 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
- Population pharmacokinetics of tacrolimus whole blood and peripheral blood mononuclear cell concentrations in stable kidney-transplanted patients.British journal of clinical pharmacology · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
aimTherapeutic drug monitoring of tacrolimus based on whole blood drug concentrations is routinely performed. The concentration of tacrolimus in peripheral blood mononuclear cells (PMBCs) is likely to better reflect drug exposure at the treatment target site. We aimed to describe the relationship between tacrolimus whole blood and PBMC concentrations, and the influence of patient characteristics on this relationship by developing a population pharmacokinetic model.
methodsWe prospectively enrolled 63 stable adult kidney-transplanted patients and collected dense (12-h, n = 18) or sparse (4-h, n = 45) pharmacokinetic profiles of tacrolimus. PBMCs were isolated from whole blood (Ficoll density gradient centrifugation), and drug concentrations in whole blood and PBMCs were analysed using liquid chromatography-mass spectrometry. Patient genotype (CYP3A4/5, ABCB1, NR1I2) was assessed with PCR. Population pharmacokinetic modelling and statistical evaluation was performed using NONMEM.
resultsTacrolimus whole blood concentrations were well described using a two-compartment pharmacokinetic model with a lag-time and first-order absorption and elimination. Tacrolimus PBMC concentrations were best estimated from whole blood concentrations with the use of a scaling factor, the ratio of whole blood to PBMC concentrations (R
conclusionTacrolimus PBMC concentration could not be accurately predicted from whole blood concentrations and covariates because of significant residual unexplained variability in the distribution of tacrolimus into PBMCs and may need to be measured directly if required for future studies.
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