Correlation between pharmacokinetics and pharmacodynamics of mycophenolic acid in liver transplant patients.
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.
Minmin
Shi
S
Center of Organ Transplantation, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, PR China.
Zhidong
Gu
G
Hao
Chen
C
Weixia
Zhang
Z
Baiyong
Shen
S
Bing
Chen
C
Chuan
Shen
S
Xiaxing
Deng
D
Xi
Zhan
Z
D000293:Adolescent; D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D044967:Serum; D013601:T-Lymphocytes / Q000187:drug effects; D055815:Young Adult
D001798:Blood Proteins; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid