Free prednisolone pharmacokinetics predicted from total concentrations in patients with inflammatory – immunonologic conditions. (21st November 2019)

• Record Type: Journal Article
• Authors: Mangin, Olivier; Zheng, Yi; Bouazza, Naïm; Foissac, Frantz; Benaboud, Sihem; Lui, Gabrielle; Hirt, Déborah; Mouthon, Luc; Tréluyer, Jean‐Marc; Urien, Saïk
• Is Part Of: Fundamental & clinical pharmacology. Volume 34:Number 2(2020)
• Page Start: 270
• Page End: 278
• Publication Date: 2019-11-21
• Subjects: corticosteroid binding globulin -- lupus -- myositis -- pharmacokinetics -- population pharmacokinetics -- prednisolone -- prednisone -- rheumatoid arthritis -- scleroderma -- vasculitis; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/fcp.12515
• Languages: English
• ISSNs: 0767-3981

Abstract

Abstract: Prednisone is an anti‐inflammatory drug widely used in internal medicine and rheumatology, but dosing remains empirical. The active metabolite of prednisone is free prednisolone. The aim of this work was to build a population pharmacokinetic (PK) model that can predict free prednisolone concentrations in patients with inflammatory/immunologic conditions.A total of 107 patients from the department of internal medicine of Cochin hospital provided 343 observations. Blood samples drawn for biological analyses were used for drug determination. Total plasma prednisolone concentrations were measured by liquid chromatography‐mass spectrometry, and the data were modelled using Monolix. The pharmacokinetics was ascribed a one‐compartment open model with three transit compartments standing for the absorption and metabolism process. The model used predicts free concentrations that served to derive total concentrations given published binding constants. Only size parameters influenced the pharmacokinetics. Free prednisolone CLU / F and V U / F, scaled allometrically on lean body weight, were, respectively, 26.7 L/h and 94.3 L for 50 kg LBW. CLU / F interindividual variability was 0.20. The additive and proportional residual variabilities were, respectively, 4.3 µg/L and 0.20. The results point out some dosing issues, that is the possibility of under‐ or over‐dosage in thin or overweight patients respectively.