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
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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