Lower dosing of enteric-coated mycophenolate sodium (Myfortic) can achieve target mycophenolic acid exposure rapidly in most Chinese renal transplant patients: a pilot study

Abstract

There are few pharmacokinetic data for enteric-coated mycophenolate sodium (EC-MPS) in Chinese kidney transplant recipients. Previously, we demonstrated that patients with 540mg EC-MPS reached target exposure on day 4 after transplantation. The aim of this study was further to confirm that mycophenolic acid (MPA) delivery with a daily total dose 1080mg EC-MPS is adequate during the early-phase posttransplantation and preliminarily assess the pharmacokinetics after a single dose and multiple doses of EC-MPS in Chinese live-donor kidney transplant recipients. Twelve patients (eight men and four women, mean age 41.3±6.78years) treated with EC-MPS, cyclosporine and corticosteroids were included in this study. Patients received a single oral dose of EC-MPS 540mg, then 540mg twice daily. MPA concentrations were measured by high-performance liquid chromatography. Twelve-hour pharmacokinetic profiles were obtained after the single oral dose and multiple doses on day 4 postoperation. The pharmacokinetic parameters were compared between a single dose and multiple doses. By using multiple stepwise regression analysis, we obtained two predictive equations of MPA systemic exposure. Bland-Altman analysis was developed to test agreement between the observed MPA area under the concentration-time curve (AUC) and the predicted MPA AUC. The mean (range) MPA AUC was 42±14.67 (29.29-75.95) mg/lh after the first dose, and 44.72±14.57 (32.06-80.79) mg/lh on day 4 after operation. MPA exposure provided by a single dose and multiple doses were similar (p>0.05). The best equations obtained were the following: 20.003+1.181C6h +7.22C8h (r=0.936) and 17.023+3.11C1h +1.245+4.988C8h (r=0.964). These equation models showed an optimal agreement between the observed MPA AUC and the predicted MPA AUC. Lower dosing of EC-MPS, compared with the standard dose (720mg twice daily), may provide enough MPA exposure for Chinese live-donor kidney transplant patients on day 4. Given that the MPA exposure by AUC correlates with the incidence of acute rejection episodes and transplant vasculopathy, the present findings may have clinical implications, and the optimum dose range of EC-MPS for patients in all ranges of body weight should also be determined.