Please use this identifier to cite or link to this item:
Title: Influence of the circadian timing system on Tacrolimus pharmacokinetics and pharmacodynamics after kidney transplantation
Author: Fontova, Pere
Colom Codina, Helena
Rigo Bonnin, Raúl
van Merendonk, Lisanne
Vidal Alabró, Anna
Montero, Nuria
Melilli, Edoardo
Meneghini, Maria
Manonelles, Anna
Cruzado, Josep Ma.
Torras Ambròs, Joan
Grinyó Boira, Josep M.
Bestard Matamoros, Oriol
Lloberas Blanch, Núria
Keywords: Ritmes circadiaris
Trasplantament renal
Circadian rhythms
Kidney transplantation
Issue Date: 17-Mar-2021
Publisher: Frontiers Media
Abstract: Introduction: Tacrolimus is the backbone immunosuppressant after solid organ transplantation. Tacrolimus has a narrow therapeutic window with large intra- and inter-patient pharmacokinetic variability leading to frequent over- and under-immunosuppression. While routine therapeutic drug monitoring (TDM) remains the standard of care, tacrolimus pharmacokinetic variability may be influenced by circadian rhythms. Our aim was to analyze tacrolimus pharmacokinetic/pharmacodynamic profiles on circadian rhythms comparing morning and night doses of a twice-daily tacrolimus formulation. Methods: This is a post-hoc analysis from a clinical trial to study the area under curve (AUC) and the area under effect (AUE) profiles of calcineurin inhibition after tacrolimus administration in twenty-five renal transplant patients. Over a period of 24 h, an intensive sampling (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 15, 20, and 24 h) was carried out. Whole blood and intracellular tacrolimus concentrations and calcineurin activity were measured by UHPLC-MS/MS. Results: Whole blood and intracellular AUC12-24 h and Cmax achieved after tacrolimus night dose was significantly lower than after morning dose administration (AUC0-12 h) (p < 0.001 for both compartments). AUE0-12 h and AUE12-24 h were not statistically different after morning and night doses. Total tacrolimus daily exposure (AUC0-24 h), in whole blood and intracellular compartments, was over-estimated when assessed by doubling the morning AUC0-12 h data. Conclusion: The lower whole blood and intracellular tacrolimus concentrations after night dose might be influenced by a distinct circadian clock. This significantly lower tacrolimus exposure after night dose was not translated into a significant reduction of the pharmacodynamic effect. Our study may provide conceptual bases for better understanding the TDM of twice-daily tacrolimus formulation.
Note: Reproducció del document publicat a:
It is part of: Frontiers in Pharmacology, 2021, vol. 12
Related resource:
ISSN: 1663-9812
Appears in Collections:Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
707698.pdf1.32 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons