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Current Drug Research Reviews

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ISSN (Print): 2589-9775
ISSN (Online): 2589-9783

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Research Article

Suspicious of Acute Kidney Graft Rejection: Tacrolimus Pharmacokinetics Under Methylprednisolone Therapy

Author(s): Nadielle Silva Bidu, Ricardo José Costa Mattoso, Otávio Augusto Carvalho de Oliveira Santos, Izabel Almeida Alves, Bruno José Dumêt Fernandes and Ricardo David Couto*

Volume 16, Issue 3, 2024

Published on: 12 October, 2023

Page: [403 - 411] Pages: 9

DOI: 10.2174/0125899775266172231004074317

Price: $65

Abstract

Background: Acute rejection remains one of the main complications in the first months after transplantation and may influence long-term outcomes. Tacrolimus has proven its usefulness in solid organ transplants and its monitoring through the application of pharmacokinetic concepts to optimize individual drug therapy.

Objective: This research proposes to evaluate the tacrolimus pharmacokinetic parameters in patients suspected of acute kidney graft rejection under methylprednisolone pulse therapy.

Methods: Eleven adult tacrolimus-treated renal recipients were selected from a prospective, single-arm, single-center cohort study, with suspicion of acute rejection although in use of methylprednisolone pulses therapy. They were followed up for three months posttransplantation, being tacrolimus trough serum concentrations determined using a chemiluminescent magnetic immunoassay, and pharmacokinetic parameters were estimated by using a nonlinear mixed-effects model implemented by Monolix 2020R1. A tacrolimus trough serum concentration range of 8 to 12 ng.mL-1 was considered therapeutic.

Results: Six patients showed acute cellular rejection, and two of them in addition had an antibody- mediated rejection. Tacrolimus trough serum concentration was below the reference range in eight patients. Most patients showed a high tacrolimus concentration intrapatient and pharmacokinetic parameters variability.

Conclusion: The obtained pharmacokinetics parameters helped in understanding the kidney recipient patients’ tacrolimus behavior, assisting in the improvement of individual drug therapy and reducing the risk of acute rejection episodes.

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Graphical Abstract

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