Abstract
Background
Despite use of a lower mycophenolate dose in Thai kidney transplant patients, acceptable graft and patient outcomes can be achieved. We therefore examined the pharmacokinetics of mycophenolic acid (MPA) by area under the curve (AUC) and investigated genetic contribution in mycophenolate metabolism in this population.
Methods
Kidney transplant recipients with stable graft function who were receiving mycophenolate mofetil 1,000 mg/d in combination with either cyclosporine or tacrolimus, and prednisolone were studied. The MPA concentration was measured by fluorescence polarization immunoassay (FPIA), at predose and 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after dosing. Genetic polymorphisms in UGT1A8, UGT1A9, and UGT2B7 were examined by denaturing high-performance liquid chromatography (DHPLC)-based single-base extension (SBE) analysis.
Results
A total 138 patients were included in study. The mean AUC was 39.49 mg-h/L (28.39–89.58 mg-h/L), which was in the therapeutic range. The correlation between the predose MPA concentration and AUC was poor. The mean AUC in the tacrolimus group was higher than that in the cyclosporine group. Polymorphisms in UGT2B7 showed significant association with AUC.
Conclusion
Most of our patients with reduced mycophenolate dose had the AUC within the therapeutic range. Genetic polymorphisms in UGT2B7 may play a role in MPA metabolism in Thai kidney transplant patients.
Keywords:
Acknowledgments
We wish to thank all the patients for their cooperation and participation in this study.
This work was supported by funding from Siriraj Research Development Grant, Siriraj Kidney Transplant Grant, Siriraj Core Research Facility, and the Thai Transplantation Society.
Author contributions
Manop Pithukpakorn participated in research design, data analysis, and writing of the manuscript. Tiwat Tiwawanwong, Yupaporn Lalerd, and Nalinee Premasathian performed data collection and data analysis. Anunchai Assawamakin performed data analysis. Adis Tasanarong participated in research design. Wanna Thongnoppakhun participated in research design and data analysis. Attapong Vongwiwatana participated in research design, data collection, data analysis, and writing of the manuscript. All authors participated in manuscript revision, ensured data integrity and approved the final version of the manuscript.
Disclosure
The authors report no conflicts of interest in this work.