Pharmacokinetics of Prednisolone at Steady State in Young Patients With Systemic Lupus Erythematosus on Prednisone Therapy: An Open-Label, Single-Dose Study

• Published in: Clinical therapeutics 2011-10, Vol.33 (10), p.1524-1536
• Main Authors: Sagcal-Gironella, Anna Carmela P., MD, Sherwin, Catherine M.T., PhD, Tirona, Rommel G., PhD, Rieder, Michael J., MD, PhD, Brunner, Hermine I., MD, Vinks, Alexander A., PharmD, PhD
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Autoimmune diseases; Biological and medical sciences; Child; Children & youth; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug therapy; Female; Glucocorticoids - pharmacokinetics; Glucocorticoids - therapeutic use; Humans; Internal Medicine; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - diagnosis; Lupus Erythematosus, Systemic - drug therapy; Male; Medical Education; Medical research; Medical sciences; pediatric SLE; pharmacokinetics; Pharmacology. Drug treatments; prednisolone; Prednisolone - blood; Prednisolone - pharmacokinetics; prednisone; Prednisone - pharmacokinetics; Prednisone - therapeutic use; Prodrugs - pharmacokinetics; Prodrugs - therapeutic use; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Severity of Illness Index; systemic lupus erythematosus; Tandem Mass Spectrometry; Young Adult
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2011.09.015

Abstract Background Current prednisone dosing in the treatment of young patients with childhood-onset systemic lupus erythematosus (cSLE) is largely based on achieving balance between therapeutic efficacy and toxicity, with weight-based dosing a common clinical practice. Despite the widespread use of prednisone, few attempts have been made to improve its clinical dosing regimen, and response to prednisone therapy remains variable. Objective The purpose of this study was to characterize the pharmacokinetic (PK) properties of prednisolone, the metabolite of the prodrug prednisone, in cSLE patients and explore the relationship between PK properties and cSLE disease activity. Methods Blood samples were taken 1 hour before the morning prednisone dose and at 20, 40, 60, and 90 minutes, and 2, 3, 4, 6, and 9 hours from 8 patients (ages 12–28 years) after an 8-hour fast. The mean weight-adjusted daily prednisone dose, stable for at least 30 days pre-study, was 0.29 mg/kg/d. PK analysis of prednisolone was performed using noncompartmental analysis with WinNonlin. cSLE disease activity was measured using the British Isles Lupus Assessment Group index and Systemic Lupus Erythematosus Disease Activity Index. Results Mean total prednisolone AUC0–9 , prednisone CL/F at steady state, and half-life were 1094 (range, 467–2404) ng/h/mL, 11 (range, 6.7–13.7) L/hr, and 2.6 (range, 1.3–3.9) hours. Mean total prednisolone AUC0–9 normalized to prednisone dose by weight was 4361 (range, 1136–9580) ng/h/mL/mg/kg. Mean total prednisolone Cmax normalized to prednisone dose by weight was 1097 (range, 301–2211) ng/mL/mg/kg at 1.84 (range, 0.48–4) hours (Tmax ). Patients on prednisone had interindividual variability in prednisolone AUC0–9 (61% CV) and dose-adjusted AUC0–9 (58% CV). Conclusions Interindividual variability in systemic exposure to prednisolone in cSLE patients was observed.