title: Evaluation of mycophenolic acid exposure using a limited sampling strategy in renal transplant recipients.
abstract: OBJECTIVE
  While there are drug exposure equation models based on limited sampling times for mycophenolate mofetil (MMF), there are few for enteric-coated mycophenolate sodium (EC-MPS), and none that studied Chinese individuals. Our objective is to generate the optimal model equations for estimation of the mycophenolic acid (MPA) area under the plasma concentration-time curve from 0 to 12 h (MPA-AUC(0-12h)) with a limited sampling strategy (LSS) for renal transplant recipients receiving EC-MPS.
  
  
  METHODS
  The pharmacokinetics in 31 Chinese renal allograft recipients treated with EC-MPS in combination with tacrolimus and steroids were determined. The model equations were generated by multiple stepwise regression analysis for estimation of the MPA-AUC.
  
  
  RESULTS
  A total of 31 patients with an average age and weight of 37.58 ± 10.9 years and 60.9 ± 10.7 kg, respectively, were included. Mean serum creatinine and glomerular filtration rate were 112.2 ± 17.7 μmol/l and 65.6 ± 14.6 ml/min, respectively. The mean values of AUC(0-12h), pre-dose MPA trough concentration (C0), maximum concentrations (C(max)), and time to reach C(max) (T(max)) were 61.17 ± 26.39 mg·h/l (range 22.9-123.0 mg·h/l), 4.98 ± 4.65 mg/l (range 0.13-20.04 mg/l), 17.54 ± 10.67 mg/l (range 4.08-42.36 mg/l), and 5.0 ± 2.6 h (range 1.0-10.5 h), respectively. The best predictive equation for estimation of MPA-AUC(0-12h) was -3.63 + 8.35 × C4 + 17.04 × C7 + 13.74 × C12 (r(2) = 0.7491), prediction bias (PE%) was 20.9 ± 20.37, and prediction precision (APE%) was 3.66 ± 29.20.
  
  
  CONCLUSIONS
  This model provides an effective approach for estimation of full MPA-AUC(0-12h) in Chinese adult renal allograft recipients treated with EC-MPS and tacrolimus.
authors.affiliation: Department of Transplantation, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Jiawen
authors.initials: J
authors.lastname: Huang
authors.forename: Qian
authors.initials: Q
authors.lastname: Fu
authors.forename: E
authors.initials: E
authors.lastname: Chen
authors.forename: Longshan
authors.initials: L
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Changxi
authors.initials: C
authors.lastname: Wang
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013608:Tablets, Enteric-Coated; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid; D016559:Tacrolimus