Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients

Jun Zhang; Mengmeng Jia; Lihua Zuo; Na Li; Yonggang Luo; Zhi Sun; Xiaojian Zhang; Zhenfeng Zhu

doi:10.1016/j.apsb.2016.11.003

Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients

Acta Pharm Sin B. 2017 May;7(3):347-352. doi: 10.1016/j.apsb.2016.11.003. Epub 2016 Dec 10.

Authors

Jun Zhang¹, Mengmeng Jia¹, Lihua Zuo¹, Na Li¹, Yonggang Luo², Zhi Sun¹, Xiaojian Zhang¹, Zhenfeng Zhu¹

Affiliations

¹ Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
² Department of Integrated Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Abstract

The aim of the research was to investigate the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from 0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLC-UV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to 900 mg, C_max and AUC_0-12h did not increase with dose escalation. The AUC_0-12h, C_max, C₀ and T_max for the 540 720 and 900 mg doses were not significantly different, respectively (P >0.05). AUC_{0-12 h} and C_max were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC_0-12h, C_max and C₀ were considerable. Nonlinear PK relationships were found from the doses of 540-900 mg of EC-MPS.

Keywords: Enteric-coated; Human plasma; Kidney transplantation; Mycophenolate sodium; Mycophenolic acid; Nonlinear dynamics; Pharmacokinetics; UPLC-UV.