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

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. In total, 60 de novo kidney transplant recipients treated with tacrolimus and steroids were randomised to receive EC-MPS at standard dose (SD; 1440mg/day; n=28) or low dose (LD; 1080mg/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 2weeks and months 1, 3 and 6 (the LSS for three-time-point MPA AUC 0-12h (mgh/l) =15.99+0.87C1h +0.68C2h +7.85C4h ; r(2) =0.8670. The mean AUC levels at day 3 and day 5 in the SD group were significantly higher than in the LD group (57.4mg·h/l vs. 38.2mg·h/l and 59.3mg·h/l vs. 44.8mg·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 6months (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 <30mg·h/l compared with those with MPA AUC levels ≥30mg·h/l within 6months (p<0.05). Renal function, incidence of infection and haematological disorders were not significantly different in either study group. 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.