Pharmacokinetics and Pharmacodynamics of Mycophenolic Acid and Individualized Therapy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460210
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: Yano Ikuko 京都大学, 薬学研究科(研究院), 准教授 (50273446)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 免疫抑制薬 / 母集団解析 / M & S / 造血幹細胞移植 / ミコフェノール酸 / IMPDH

Outline of Final Research Achievements

The experimental data obtained from Nagase analbuminemic rats showed that the free mycophenolic acid (MPA) concentration was suitable for the biomarker of immunosuppressive effect of MPA. Simulations based on the obtained pharmacokinetic and pharmacodynamic parameters showed that the pharmacological marker IMPDH activity decreased non-linearly according to the increase in free fraction of MPA, although the area under the concentration-time curve of free MPA increased linearly.Population pharmacokinetic and pharmacodynamic analyses using clinical data obtained from hematopoietic stem cell transplant patients showed that the decreased renal failure increased the MPA concentration by the increased enterohepatic circulation of the accumulated metabolite, but scarcely affected the pharmacological effects.
In conclusion, since the pharmacodynamics of MPA was non-linear, the increased MPA concentration has a limited effect on the pharmacological effects of MPA.

Free Research Field

医療薬学