C Ding1, W Xue, P Tian, X Ding, X Pan, H Xiang, X Tian, Y Li, J Zheng. 1. 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.
Abstract
AIMS: 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. METHODOLOGY:In total, 60 de novo kidney transplant recipients treated withtacrolimus 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.
RCT Entities:
AIMS: 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. METHODOLOGY: 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.