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Title: A prospective controlled, randomized clinical trial of kidney transplant recipients developed personalized tacrolimus dosing using model-based Bayesian Prediction
Author: Lloberas Blanch, Núria
Grinyó Boira, Josep M.
Colom Codina, Helena
Vidal Alabró, Anna
Fontova, Pere
Rigo Bonnin, Raúl
Padró i Miquel, Ariadna
Bestard Matamoros, Oriol
Melilli, Edoardo
Montero Pérez, Núria
Coloma, Ana
Manonelles, Anna
Meneghini, Maria
Fava, Alex
Torras Ambròs, Joan
Cruzado, Josep Ma.
Keywords: Trasplantament renal
Estadística bayesiana
Kidney transplantation
Bayesian statistical decision
Immunosupressive agents
Issue Date: 1-Oct-2023
Publisher: Elsevier B.V.
Abstract: For three decades, tacrolimus (Tac) dose adjustment in clinical practice has been calculated empirically according to the manufacturer’s labeling based on a patient’s body weight. Here, we developed and validated a Population pharmacokinetic (PPK) model including pharmacogenetics (cluster CYP3A4/CYP3A5), age, and hematocrit. Our study aimed to assess the clinical applicability of this PPK model in the achievement of Tac Co (therapeutic trough Tac concentration) compared to the manufacturer’s labelling dosage. A prospective two-arm, randomized, clinical trial was conducted to determine Tac starting and subsequent dose adjustments in 90 kidney transplant recipients. Patients were randomized to a control group with Tac adjustment according to the manufacturer’s labeling or the PPK group adjusted to reach target Co (6-10 ng/ml) after the first steady state (primary endpoint) using a Bayesian prediction model (NONMEM). A significantly higher percentage of patients from the PPK group (54.8%) compared with the control group (20.8%) achieved the therapeutic target fulfilling 30% of the established superiority margin defined. Patients receiving PPK showed significantly less intra-patient variability compared to the control group, reached the Tac Co target sooner (5 days vs 10 days), and required significantly fewer Tac dose modifications compared to the control group within 90 days following kidney transplant. No statistically significant differences occurred in clinical outcomes. Thus, PPK-based Tac dosing offers significant superiority for starting Tac prescription over classical labeling-based dosing according to the body weight, which may optimize Tac-based therapy in the first days following transplantation.
Note: Versió postprint del document publicat a:
It is part of: Kidney International, 2023, vol. 104, num.4, p. 840-850
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ISSN: 0085-2538
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

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