title: Pharmacokinetics of prednisolone at steady state in young patients with systemic lupus erythematosus on prednisone therapy: an open-label, single-dose study.
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 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: Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
authors: Anna Carmela P
authors: AC
authors: Sagcal-Gironella
authors: Catherine M T
authors: CM
authors: Sherwin
authors: Rommel G
authors: RG
authors: Tirona
authors: Michael J
authors: MJ
authors: Rieder
authors: Hermine I
authors: HI
authors: Brunner
authors: Alexander A
authors: AA
authors: Vinks
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D011239:Prednisolone / Q000097:blood / Q000493:pharmacokinetics*; D011241:Prednisone / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011355:Prodrugs / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D011355:Prodrugs; D011239:Prednisolone; D011241:Prednisone