Pharmacokinetics Evaluation of Mycophenolic Acid and Its Glucuronide Metabolite in Chinese Renal Transplant Recipients Receiving Enteric-Coated Mycophenolate Sodium and Tacrolimus

Background: The aim of this study was to characterize the pharmacokinetics of mycophenolic acid (MPA) and MPA glucuronide (MPAG) in Chinese renal transplant patients taking enteric-coated mycophenolate sodium (EC-MPS). Limited sampling strategies (LSSs) were developed to estimate the area under the concentration curve from 0 to 12 hours (AUC(0-12h)) of total and free MPA. Another objective was to investigate the correlation between high-performance liquid chromatography (HPLC) and enzyme-multiplied immunoassay technology (EMIT) for total MPA determination. Methods: Serial blood samples were collected over 12 hours from 15 patients who were administered multiple doses of EC-MPS. LSS was developed by multiple stepwise regression analysis. Measurement by HPLC and EMIT was compared using Passing-Bablok regression and Bland-Altman analysis. Results: Normalized to 720 mg twice daily, the AUC(0-12h) of total MPA and MPAG was 43.0 +/- 17.4 and 653 +/- 329 mg.h/L, respectively, whereas the free MPA AUC(0-12h) was 1.368 +/- 0.988 mg.h/L. The free fraction of MPA was 3.01% +/- 3.15%. The combination of C-2h-C-4h-C-6h and C-2h-C-4h-C-6h-C-8h was found to be superior to estimate total and free MPA simultaneously. The EMIT showed an acceptable correlation with HPLC, with an AUC0-12h overestimation of 11.32% +/- 15.77%. Conclusions: The pharmacokinetic profile of total and free MPA and its main metabolite MPAG was examined in Chinese adult renal transplant patients receiving EC-MPS. The use of LSS to estimate individual free and total MPA exposure could be useful in optimizing patient care.