Monitoring the tacrolimus concentration in peripheral blood mononuclear cells of kidney transplant recipients
Autor: | Brenda C. M. de Winter, Dennis A. Hesselink, Yi Li, Ron H.N. van Schaik, Lin Yang, Birgit C. P. Koch, Marith I. Francke, Teun van Gelder, Carla C. Baan, Lucia E.A. de Wit |
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Přispěvatelé: | Internal Medicine, Pharmacy, Clinical Chemistry |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
medicine.medical_specialty
peripheral blood mononuclear cell Genotype therapeutic drug monitoring Urology kidney transplantation chemical and pharmacologic phenomena 030226 pharmacology & pharmacy Peripheral blood mononuclear cell Polymorphism Single Nucleotide Tacrolimus Nephrotoxicity 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being stomatognathic system Diabetes mellitus Medicine Cytochrome P-450 CYP3A Humans Pharmacology (medical) 030212 general & internal medicine Kidney transplantation pharmacogenetics Pharmacology medicine.diagnostic_test business.industry Albumin Original Articles medicine.disease Transplant Recipients stomatognathic diseases Therapeutic drug monitoring Toxicity Leukocytes Mononuclear Original Article business Immunosuppressive Agents |
Zdroj: | British Journal of Clinical Pharmacology British Journal of Clinical Pharmacology, 87(4), 1918-1929. Wiley-Blackwell Publishing Ltd |
ISSN: | 1365-2125 0306-5251 |
Popis: | Aims: Tacrolimus is a critical dose drug and to avoid under- and overexposure, therapeutic drug monitoring is standard practice. However, rejection and drug-related toxicity occur despite whole-blood tacrolimus pre-dose concentrations ([Tac]blood) being on target. Monitoring tacrolimus concentrations at the target site (within peripheral blood mononuclear cells; [Tac]cells) may better correlate with drug-efficacy. The aim of this study was to (1) investigate the relationship between [Tac]blood and [Tac]cells, (2) identify factors affecting the tacrolimus distribution in cells and whole-blood, and (3) study the relationship between [Tac]cells and clinical outcomes after kidney transplantation. Methods: A total of 175 renal transplant recipients were prospectively followed. [Tac]blood and [Tac]cells were determined at Months 3, 6 and 12 post-transplantation. Patients were genotyped for ABCB1 1199G>A and 3435C>T, CYP3A4 15389C>T, and CYP3A5 6986G>A. Data on rejection and tacrolimus-related nephrotoxicity and post-transplant diabetes mellitus were collected. Results: Correlations between [Tac]blood and [Tac]cells were moderate to poor (Spearman's r = 0.31; r = 0.41; r = 0.61 at Months 3, 6 and 12, respectively). The [Tac]cells/[Tac]blood ratio was stable over time in most patients (median intra-patient variability 39.0%; range 3.5%–173.2%). Age, albumin and haematocrit correlated with the [Tac]cells/[Tac]blood ratio. CYP3A5 and CYP3A4 genotype combined affected both dose-corrected [Tac]blood and [Tac]cells. ABCB1 was not significantly related to tacrolimus distribution. Neither [Tac]blood nor [Tac]cells correlated with clinical outcomes. Conclusions: The correlation between [Tac]blood and [Tac]cells is poor. Age, albumin and haematocrit correlate with the [Tac]cells/[Tac]blood ratio, whereas genetic variation in ABCB1, CYP3A4 and CYP3A5 do not. Neither [Tac]blood nor [Tac]cells correlated with clinical outcomes. |
Databáze: | OpenAIRE |
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