title: Which is more suitable for kidney transplantation at the early post-transplantation phase in China - low dosing or standard dosing of enteric-coated mycophenolate sodium?
abstract: OBJECTIVE
  To investigate the pharmacokinetics of enteric-coated mycophenolate sodium (EC-MPS) and the clinical outcome in kidney transplant recipients in the early post-transplantation phase. Then explain which regimen is more suitable for Chinese renal transplant recipients.
  
  
  METHODS
  In total, 60 de novo kidney transplant recipients treated with tacrolimus and steroids were randomised to receive EC-MPS at standard dose (SD; 1440 mg/day; n = 28) or low dose (LD; 1080 mg/day; n = 32). Efficacy parameters, safety and tolerability were assessed over a 6-month study period. Full mycophenolic acid (MPA) areas under the curve (AUCs) were completed on days 3 and 5, whereas a three-point limited sampling strategy (LSS) was utilised for MPA AUC assessments at 2 weeks and months 1, 3 and 6 (the LSS for three-time-point MPA AUC 0-12 h (mg h/l) = 15.99 + 0.87C1 h  + 0.68C2 h  + 7.85C4 h ; r(2)  = 0.8670.
  
  
  RESULTS
  The mean AUC levels at day 3 and day 5 in the SD group were significantly higher than in the LD group (57.4 mg·h/l vs. 38.2 mg·h/l and 59.3 mg·h/l vs. 44.8 mg·h/l, respectively, p < 0.01). There was a trend for fewer clinically diagnosed acute rejections in the SD group vs. the LD group at 6 months (7.1% vs. 12.5%). This trend was also present when acute rejection was analysed as biopsy-proven cases. There were significantly more acute rejections (all definitions) in patients with MPA AUC levels < 30 mg·h/l compared with those with MPA AUC levels ≥ 30 mg·h/l within 6 months (p < 0.05). Renal function, incidence of infection and haematological disorders were not significantly different in either study group.
  
  
  CONCLUSIONS
  Early adequate MPA exposure in renal transplant recipients can be achieved with a higher starting dose. In addition, a SD regimen was as well-tolerated as a LD regimen. Furthermore, early adequate MPA exposure significantly lowered the rate of acute rejection without compromising safety and tolerability.
authors.affiliation: Department of Renal Transplantation, Medical College of Xi'an Jiaotong University, Xi'an, China; Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China.
authors.forename: C
authors.initials: C
authors.lastname: Ding
authors.forename: W
authors.initials: W
authors.lastname: Xue
authors.forename: P
authors.initials: P
authors.lastname: Tian
authors.forename: X
authors.initials: X
authors.lastname: Ding
authors.forename: X
authors.initials: X
authors.lastname: Pan
authors.forename: H
authors.initials: H
authors.lastname: Xiang
authors.forename: X
authors.initials: X
authors.lastname: Tian
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000328:Adult; D002681:China / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D015994:Incidence; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011446:Prospective Studies; D013608:Tablets, Enteric-Coated; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid; D016559:Tacrolimus