title: Development of population PK model with enterohepatic circulation for mycophenolic acid in patients with childhood-onset systemic lupus erythematosus.
abstract: OBJECTIVE
  This study aimed to develop a population pharmacokinetic (PK) enterohepatic recycling model for MPA in patients with childhood-onset systemic lupus erythematosus (cSLE).
  
  
  METHODS
  MPA concentration-time data were from outpatients on stable oral mycophenolate mofetil (MMF) and collected under fasting conditions, with standardized meals (1 and 4 h post-dose). Sampling times were pre-dose, 20, 40 min, 1, 1.5, 2, 3, 4, 6 and 9 h, post dose. The population PK analysis simultaneously modelled MPA and 7-O-MPA-β-glucuronide (MPAG) concentrations using nonlinear mixed effect modelling.
  
  
  RESULTS
  PK analysis included 186 MPA and MPAG concentrations (mg l(-1)) from 19 patients. cSLE patients, age range 10-28 years, median 16.5 years were included. Mean ± SD disease duration was 3.8 ± 3.7 years. The final PK model included a gallbladder compartment for enterohepatic recycling and bile release time related to meal times, with first order absorption and single series of transit compartments. The PK estimates for MPA were CL(1) /F 25.3 l h(-1), V(3) /F 20.9 l, V(4) /F 234 l and CL(2) /F 19.8 l h(-1).
  
  
  CONCLUSIONS
  The final model fitted the complex processes of absorption and enterohepatic circulation (EHC) in those treated with MMF for cSLE and could be applied in Bayesian dose optimization algorithms.
authors: Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
authors: Catherine M T
authors: CM
authors: Sherwin
authors: Anna Carmela P
authors: AC
authors: Sagcal-Gironella
authors: Tsuyoshi
authors: T
authors: Fukuda
authors: Hermine I
authors: HI
authors: Brunner
authors: Alexander A
authors: AA
authors: Vinks
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001499:Bayes Theorem; D002648:Child; D004764:Enterohepatic Circulation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D020719:Glucuronides / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007166:Immunosuppressive Agents; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D020719:Glucuronides; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D009173:Mycophenolic Acid