title: Population pharmacokinetics of mycophenolate mofetil in Thai lupus nephritis patients.
abstract: OBJECTIVE
  Mycophenolic acid (MPA) has become the first-line drug therapy for proliferative lupus nephritis, a common and serious complication of systemic lupus erythematosus. Although a sufficient MPA exposure is required, a high interindividual variability in the pharmacokinetics of MPA has been observed. The knowledge of MPA pharmacokinetics in lupus nephritis patients is limited, especially in Asian patients. This study aimed to develop a population pharmacokinetic model for MPA and determine the population pharmacokinetic parameters and their interindividual variability in Thai patients with lupus nephritis.
  
  
  METHODS
  A total of 112 MPA plasma concentrations from 14 adult lupus nephritis patients (International Society of Nephrology/Renal Pathology Society Class III/IV) receiving mycophenolate mofetil were included in this study. The data was analyzed using NONMEM. The model evaluation was performed by the bootstrap approach and visual predictive check.
  
  
  RESULTS
  A two-compartment model with a lag time best described the data. The estimated mean apparent clearance (CL/F) was 14.5 l/h with an interindividual variability of 45.2%. The estimated mean CL/F was found to be lower than the values previously reported. The estimated mean apparent volume of the central compartment was 12.2 l with an interindividual variability of 166%. None of the covariates were found to significantly influence MPA pharmacokinetics.
  
  
  CONCLUSIONS
  In this study, a population pharmacokinetic model of MPA in severe lupus nephritis patients was successfully developed. The mean pharmacokinetic parameters were estimated and a high interindividual variability of MPA in this population was observed. This provides evidence to show that individualizing dosage regimens in this population is crucial. The model developed in this study could be used to obtain initial information for MPA dose adjustments in Thai and Asian patients with lupus nephritis. Further studies are required to validate the results and clarify the influence of covariates on MMF pharmacokinetics.
authors.affiliation: Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Baralee
authors.initials: B
authors.lastname: Punyawudho
authors.forename: Paungpaga
authors.initials: P
authors.lastname: Lertdumrongluk
authors.forename: Poorichaya
authors.initials: P
authors.lastname: Somparn
authors.forename: Wonngarm
authors.initials: W
authors.lastname: Kittanamongkolchai
authors.forename: Opas
authors.initials: O
authors.lastname: Traitanon
authors.forename: Yingyos
authors.initials: Y
authors.lastname: Avihingsanon
authors.forename: Somratai
authors.initials: S
authors.lastname: Vadcharavivad
mesh_terms: D000328:Adult; D044466:Asian People; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008181:Lupus Nephritis / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology; D008297:Male; D008954:Models, Biological; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D013785:Thailand / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid