Premium
Correlation Between Pharmacokinetics and Pharmacodynamics of Mycophenolic Acid in Liver Transplant Patients
Author(s) -
Minmin Shi,
Zhidong Gu,
Hao Chen,
Weixia Zhang,
Baiyong Shen,
Bing Chen,
Chuan Shen,
Xiaxing Deng,
Xi Zhan
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009359526
Subject(s) - mycophenolate , mycophenolic acid , pharmacokinetics , pharmacodynamics , dosing , pharmacology , area under the curve , chemistry , plasma concentration , medicine , urology , transplantation
This study investigated the relationship between pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA) in liver transplant patients receiving mycophenolate mofetil (MMF). Total and free plasma MPA concentrations were determined by high‐performance liquid chromatography before MMF dose and at 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after dosing in 27 patients. The inhibitory capacity of serum MPA on proliferation of CEM cells was monitored at 0, 1, and 2 hours. The concentration of free MPA at 0, 1, and 2 hours (C 0h , C 1h , C 2h ) and the area under the concentration‐time curve at 0 to 12 hours (AUC 0‐12h ) of free MPA were significantly related to those of total MPA (P < .05). C 1h and C 2h of total and free MPA were conversely related with the rate of proliferation of CEM cells (P < .05). At 1 and 2 hours after an MMF dose, the percentage of CEM cell proliferation was below 40% in the majority of patients compared with the percentage before dosing. Thus, there was a significant relationship between total and free plasma MPA concentrations in liver transplant patients. After MMF dose, the inhibitory capacity of serum MPA on proliferation of CEM cells was enhanced significantly. This effect was related greatly to MPA concentrations.