Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients-The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy.

Magdalena Bodnar-Broniarczyk,Katarzyna Czerwińska,Ryszard Marszałek,Magdalena Durlik,Tomasz Pawiński,Teresa Bączkowska

doi:10.3390/pharmaceutics13101576

Magdalena Bodnar-Broniarczyk, Katarzyna Czerwińska + Show 4 more

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https://doi.org/10.3390/pharmaceutics13101576

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Journal: Pharmaceutics	Publication Date: Sep 28, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: Medical University of Warsaw

Abstract

Tacrolimus (TAC) has a narrow therapeutic index and highly variable pharmacokinetic characteristics. Close monitoring of the TAC concentrations is required in order to avoid the risk of acute rejection or adverse drug reaction. The results in some studies indicate that inter-tissue TAC concentrations can be a better predictor with regards to acute rejection episode than TAC concentration in whole blood. Therefore, the aim of the study was to assess the correlation between dosage, blood, hepatic and kidney tissue concentration of TAC measured by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and clinical outcomes in a larger cohort of 100 liver and renal adult transplant recipients. Dried biopsies were weighed, mechanically homogenized and then the samples were treated with a mixture of zinc sulfate—acetonitrile to perform protein precipitation. After centrifugation, the extraction with tert-butyl methyl ether was performed. The analytical range was proven for TAC tissue concentrations of 10–400 pg/mg. The accuracy and precision fell within the acceptance criteria for intraday as well as interday assay. There was no correlation between dosage, blood (C0) and tissue TAC concentrations. TAC concentrations determined in liver and kidney biopsies ranged from 8.5 pg/mg up to 160.0 pg/mg and from 7.1 pg/mg up to 215.7 pg/mg, respectively. To the best of our knowledge, this is the first LC-MS/MS method for kidney and liver tissue TAC monitoring using Tac13C,D2 as the internal standard, which permits measuring tissue TAC concentrations as low as 10 pg/mg.

Highlights

Therapeutic Drug Monitoring (TDM) of immunosuppressive agents is an integral part of effective pharmacotherapy of patients after organ transplantation [1]
The aim of the study was to assess the correlation between whole blood, hepatic and kidney tissue concentrations of TAC measured by a validated LC-MS/MS and clinical outcome in a cohort of 100 liver and renal transplant recipients
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Summary

Introduction

Therapeutic Drug Monitoring (TDM) of immunosuppressive agents is an integral part of effective pharmacotherapy of patients after organ transplantation [1]. Immunosuppressive agents are critical dose drugs exhibiting desirable therapeutic effects with an acceptable tolerability within a narrow range of blood concentrations. The correlation between blood drug concentrations and clinical outcomes is an important factor supporting the use of TDM. Despite plasma and whole blood being used in routine TDM as the most popular matrices, they have a number of limitations [2]: venous blood sampling, centrifugation and shipment at low temperatures. Drug concentrations in plasma or blood rarely reflect drug or metabolite level in tissues or cells. Drug concentrations in plasma or blood rarely reflect drug or metabolite level in tissues or cells. 4.0/).

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