title: Pharmacokinetics of enteric-coated mycophenolate sodium in Chinese renal transplantation recipients.
abstract: BACKGROUND
  Mycophenolic acid (MPA) as an anti-proliferative immune-suppressive agent is used in the majority of immunosuppressive regimens in solid organ transplantation. This study aimed to investigate the pharmacokinetic (PK) characteristics of enteric-coated mycophenolate sodium (EC-MPS) and area under the curve (AUC) from 0 to 12 hours with limited sampling strategies (LSSs) in Chinese renal transplant recipients.
  
  
  METHODS
  This study was conducted in 10 Chinese renal transplant patients receiving living donor and treated with EC-MPS, cyclosporine, and corticosteroids. MPA concentrations were measured by enzyme multiplied immunoassay technique (EMIT). Whole 12-hour PK profiles were obtained on Day 4 after operation. LSSs with jackknife technique, multiple stepwise regression analysis, and Bland-Altman analysis were developed to estimate MPA AUC.
  
  
  RESULTS
  The mean maximum plasma concentration, the mean time for it to reach peak (T(max)), and the mean MPA AUC were (11.38 ± 2.49) mg/L, (4.85 ± 3.32) hours, and (63.19 ± 13.54) mg×h×L(-1), respectively. Among the 10 profiles, MPA AUC of four patients was significantly higher than that of the other six patients, and the corresponding T(max) was significantly longer than that of the other six patients. No patient exhibited a second peak caused by enterohepatic recirculation. The best models were as follows: 27.46 + 0.94C(3) + 3.24C(8) + 2.81C(10) (r(2) = 0.972), which was used to predict AUC of fast metabolizer with a mean prediction error (MPE) of -0.21% and a mean absolute prediction error (MAE) of 2.59%; 36.65 + 3.08C(8) + 5.30C(10) - 4.04C(12) (r(2) = 0.992), which was used to predict AUC of slow metabolizer with a MPE of 0.58% and a MAE of 1.95%.
  
  
  CONCLUSIONS
  The PKs of EC-MPS had a high variability among Chinese renal transplant recipients. The preliminary PK data indicated the existence of slow and fast metabolizer. These findings may be associated with the enterohepatic recirculation.
authors.affiliation: Department of Pharmacology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Qiu
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Hu
authors.forename: Xiao-Bei
authors.initials: XB
authors.lastname: Li
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Gong
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Liu
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D016572:Cyclosporine; D009173:Mycophenolic Acid