title: Pharmacokinetic study of oral prednisolone compared with intravenous methylprednisolone in patients with juvenile dermatomyositis.
abstract: OBJECTIVE
  To determine areas under the curve (AUCs) of oral prednisolone (OP) and intravenous methylprednisolone (IVMP) in patients with juvenile dermatomyositis (DM) and assess the association with nailfold end-row loops (ERLs). Patients with active disease have fewer ERLs that possibly occur in the gastrointestinal tract, impairing absorption of oral medications.
  
  
  METHODS
  Six patients with juvenile DM received 50 mg/m(2) of OP (day 1) and IVMP (day 2). Blood was drawn at baseline and at 5, 15, 30, 45, 60, and 90 minutes, and hourly (hours 2-8) after each dose. Samples were analyzed by reverse-phase high-performance liquid chromatography for levels of prednisolone and methylprednisolone. AUCs of OP and IVMP were determined by the trapezoid method; pharmacokinetic parameters were obtained using noncompartmental and compartmental analysis. ERLs were determined from freeze-frame video microscopy and nailfold capillaroscopy.
  
  
  RESULTS
  There was a trend toward significance in difference in mean AUC of IVMP (116.72 microg x ml/hour) compared with OP (65.16 microg x ml/hour; P = 0.059). Mean peak concentration was higher for IVMP (34.49 microg/ml) than OP (7.08 microg/ml); mean half-life was shorter for IVMP (1.90 hours) than OP (2.36 hours). There was an inverse association between DeltaAUCs (IVMP AUC - OP AUC) and ERLs (R = -0.68, P = 0.044).
  
  
  CONCLUSIONS
  Patients with juvenile DM and ERL loss may have decreased bioavailability of OP compared with IVMP. This can provide the rationale for greater efficacy of IVMP in patients with active vasculopathy of juvenile DM. Further studies investigating the pharmacokinetics and pharmacodynamics of high-dose IVMP need to be performed in patients with juvenile DM.
authors.affiliation: Wake Forest University Baptist Medical Center, Pediatric Rheumatology, Winston-Salem, North Carolina 27157, USA. krouster@wfubmc.edu
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Rouster-Stevens
authors.forename: Aneel
authors.initials: A
authors.lastname: Gursahaney
authors.forename: Ka-Leung
authors.initials: KL
authors.lastname: Ngai
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Daru
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Pachman
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002196:Capillaries; D002648:Child; D003882:Dermatomyositis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011239:Prednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000893:Anti-Inflammatory Agents; D011239:Prednisolone; D008775:Methylprednisolone