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.