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. 2025 Oct;91(10):2854-2864.
doi: 10.1002/bcp.70103. Epub 2025 May 23.

Population pharmacokinetic modelling of prednisolone in systemic lupus erythematosus patients: Analysis of exposure and disease activity

Naïm Bouazza  1   2   3 , Michaela Semeraro  1   3 , Gabrielle Lui  1   3   4 , Léo Froelicher-Bournaud  1   4 , Laure Choupeaux  2 , Jean-Marc Treluyer  1   2   3   4 , Sihem Benaboud  1   4 , Joelle Terzic  5 , Eric Hachulla  6 , Philippe Remy  7 , Jérôme Harambat  8 , Alexandre Karras  9 , Caroline Rousset-Rouviere  10 , Anne Jolivot  11 , Zahir Amoura  12 , Eric Daugas  13 , Aurélie Hummel  14 , Rémi Salomon  15 , Jean-Christophe Lega  16 , Stéphane Decramer  17 , Alexandre Belot  18 , Delphine Gobert  19 , Nathalie Costedoat-Chalumeau  20 , Stanislas Faguer  21 , Isabelle Melki  22 , Noémie Jourde-Chiche  23 , Brigitte Bader-Meunier  24
Affiliations

Population pharmacokinetic modelling of prednisolone in systemic lupus erythematosus patients: Analysis of exposure and disease activity

Naïm Bouazza et al. Br J Clin Pharmacol. 2025 Oct.

Abstract

Aims: Prednisone is a widely used glucocorticoid in the treatment of lupus, although its dosing is often determined empirically. Prednisolone, the active metabolite of prednisone, is found in its free form in the serum. The goal of this study was to develop a population pharmacokinetic model in patients with systemic lupus erythematosus (SLE) to forecast free prednisolone concentrations and its association with disease activity.

Methods: A total of 66 active SLE patients (adults and children) were included, and followed up prospectively (242 observations available). Plasma prednisolone concentrations were assessed using liquid chromatography-mass spectrometry, and the data were analysed using Monolix software. The pharmacokinetic model was a one-compartment open model with absorption lag time representing the delay for both absorption and metabolism from inactive (prednisone) to active form (prednisolone). This model predicted free concentrations, which were then used to calculate total concentrations based on established binding constants.

Results: Free prednisolone clearance (CLu/F) and volume of distribution (Vu/F) were scaled allometrically to body weight. The typical population estimates (95% confidence interval) were 54 (48-62) L/h/70 kg and 235 (203-274) L/70 kg, respectively. Additionally, the bioavailability parameter was found to decrease non-linearly with the dose. Prednisolone cumulative exposure was not different between patients who responded at 3 months and those who did not.

Conclusions: Robust pharmacokinetic targets are not yet clearly defined regarding toxicity or efficacy and are warranted in order to make a valuable contribution to prednisolone therapeutic drug monitoring in the context of SLE.

Keywords: disease activity; population pharmacokinetics.

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Conflict of interest statement

The authors have no competing interests to declare in relation to this work.

Figures

FIGURE 1
FIGURE 1
Prediction corrected visual predictive check (pcVPC). The lines show the 10th, 50th and 90th percentiles of observed data. The areas represent the 90% confidence interval around the simulated percentiles. Light‐blue filled circles stand for pc‐observed prednisolone concentrations in responder patients, light‐red filled circles stand for pc‐observed prednisolone concentrations in non‐responder patients and stars stand for below limit of quantification data.
FIGURE 2
FIGURE 2
Cumulative total (left) and free (right) prednisolone AUC0‐M3 between the responders and non‐responders.
FIGURE 3
FIGURE 3
Kaplan‐Meier representation for adverse event‐free probability.
See this image and copyright information in PMC

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