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 AUC(0-9), 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 AUC(0-9) normalized to prednisone dose by weight was 4361 (range, 1136-9580) ng/h/mL/mg/kg. Mean total prednisolone C(max) normalized to prednisone dose by weight was 1097 (range, 301-2211) ng/mL/mg/kg at 1.84 (range, 0.48-4) hours (T(max)). Patients on prednisone had interindividual variability in prednisolone AUC(0-9) (61% CV) and dose-adjusted AUC(0-9) (58% CV). CONCLUSIONS: Interindividual variability in systemic exposure to prednisolone in cSLE patients was observed.
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 AUC(0-9), 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 AUC(0-9) normalized to prednisone dose by weight was 4361 (range, 1136-9580) ng/h/mL/mg/kg. Mean total prednisolone C(max) normalized to prednisone dose by weight was 1097 (range, 301-2211) ng/mL/mg/kg at 1.84 (range, 0.48-4) hours (T(max)). Patients on prednisone had interindividual variability in prednisolone AUC(0-9) (61% CV) and dose-adjusted AUC(0-9) (58% CV). CONCLUSIONS: Interindividual variability in systemic exposure to prednisolone in cSLE patients was observed.
Authors: Azrin N Abd Rahman; Susan E Tett; Halim A Abdul Gafor; Brett C McWhinney; Christine E Staatz Journal: Br J Clin Pharmacol Date: 2015-07-02 Impact factor: 4.335