Protein binding study of mycophenolate mofetil, a new immunosuppressant, in human plasma and pharmacokinetics in renal transplant patients

被引:0
作者
Sugioka, N
Koyama, H
Uno, A
Ohta, T
Takada, K
Yasumura, T
Oka, T
机构
关键词
mycophenolate mofetil; mycophenolic acid; protein binding; pharmacokinetics;
D O I
暂无
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mycophenolate mofetil (MPM): a new immunosuppressant, is a morpholinoethyl ester of mycophenolic acid (MPA). The pharmacokinetics of MPA after multiple MPM administration to renal transplant patients and in vitro protein binding of MPA in human serum were studied. In in vitro binding study using human plasma, the unbound fraction of MPA was 2.5 +/- 0.7% (total MPA concentration was 100 mu g/ml). There was no change in the unbound fraction of MPA (about 1.5%) at a concentration range less than 300 mu M (96.1 mu g/ml) of total plasma MPA concentration. However, over 300 mu M, the unbound fraction of MPA increased depending on its total concentration. Scatchard plots for MPA binding to human serum albumin were biphasic, suggesting MPA has at least two specific binding sites on albumin molecule. The unbound fraction of MPA in human plasma was significantly increased by adding furosemide or lansoprazole. In renal transplant patients who received oral MPM medication at doses of 1000, 2000, 3000 and 1000 mg/day, the peak plasma concentrations of MPA were 4.4, 4.5, 10.6 and 15.1 mu g/ml, respectively. The mean peak times were 0.5 similar to 2h. The terminal elimination half-lives were 17.3 (1000mg/day), 13.2 (3000mg/day) and 15.2 (4000mg/day) h. The plasma concentration of the main metabolite of MPA, phenolic grucuronide, was ten times higher than plasma MPA concentration. The area under the plasma MPA concentration-time curve was correlated to the administerd dose. The plasma trough level of MPA did not reflect the administerd dose of MPM. MPM medication did not affect the pharmacokinetic parameters of cyclosporin A which concomitantly used for immunosuppressive therapy.
引用
收藏
页码:33 / 42
页数:10
相关论文
共 50 条
[41]   Benefits of conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in pediatric renal transplant patients with stable graft function [J].
Meneses, Rejane de Paula ;
Kotsifas, Cecilia Halusch .
PEDIATRIC TRANSPLANTATION, 2009, 13 (02) :188-193
[42]   Mycophenolate mofetil maintenance therapy in renal transplant patients: long-term results of the TranCept STAY study [J].
Heemann, Uwe ;
Kliem, Volker ;
Budde, Klemens ;
Hamza, Amir ;
Juergensen, Jan Steffen ;
Juarez, Federico ;
Arns, Wolfgang ;
Rath, Thomas ;
Haller, Hermann .
CLINICAL TRANSPLANTATION, 2012, 26 (06) :919-926
[43]   Mycophenolic Acid Exposure in High- and Low-Weight Renal Transplant Patients After Dosing With Mycophenolate Mofetil in the Opticept Trial [J].
Kaplan, Bruce ;
Gaston, Robert S. ;
Meier-Kriesche, Herwig-Ulf ;
Bloom, Roy D. ;
Shaw, Leslie M. .
THERAPEUTIC DRUG MONITORING, 2010, 32 (02) :224-227
[44]   Characterizing the role of enterohepatic recycling in the interactions between mycophenolate mofetil and calcineurin inhibitors in renal transplant patients by pharmacokinetic modelling [J].
Cremers, S ;
Schoemaker, R ;
Scholten, E ;
den Hartigh, J ;
König-Quartel, J ;
van Kan, E ;
Paul, L ;
de Fijter, J .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2005, 60 (03) :249-256
[45]   RELATE: Relationship of limited sampling strategy and adverse effects of mycophenolate mofetil in pediatric renal transplant patients [J].
Berger, Iona ;
Haubrich, Kathryn ;
Ensom, Mary H. H. ;
Carr, Roxane .
PEDIATRIC TRANSPLANTATION, 2019, 23 (02)
[46]   Differential profiles of adverse events associated with mycophenolate mofetil between adult and pediatric renal transplant patients [J].
Hosohata, Keiko ;
Matsuoka, Etsuko ;
Inada, Ayaka ;
Oyama, Saki ;
Niinomi, Iku ;
Mori, Yasuhiro ;
Yamaguchi, Yuki ;
Uchida, Mayako ;
Iwanaga, Kazunori .
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2018, 46 (11) :4617-4623
[47]   Preliminary experience with mycophenolate mofetil for preservation of renal function in cardiac transplant patients with documented cyclosporine nephrotoxicity [J].
Al-Aly, Z ;
Sachdeva, A ;
Ashley, JMP ;
Bastani, B .
NEPHROLOGY, 2006, 11 (02) :151-155
[48]   Four cases of red blood cell aplasia in association with the use of mycophenolate mofetil in renal transplant patients [J].
Engelen, W ;
Verpooten, GA ;
Van der Planken, M ;
Helbert, MF ;
Bosmans, JL ;
De Broe, ME .
CLINICAL NEPHROLOGY, 2003, 60 (02) :119-124
[49]   Ex vivo lymphocyte proliferative function is severely inhibited in renal transplant patients on mycophenolate mofetil treatment [J].
Hutchinson, P ;
Jose, M ;
Atkins, RC ;
Holdsworth, SR .
TRANSPLANT IMMUNOLOGY, 2004, 13 (01) :55-61
[50]   Improved Gastrointestinal Symptoms and Quality of Life after Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium in Renal Transplant Patients Receiving Tacrolimus [J].
Hwang, Hyeon Seok ;
Hyoung, Bok Jin ;
Kim, Sol ;
Oh, Ha Young ;
Kim, Yon Su ;
Kim, Jung Kyung ;
Kim, Yeong Hoon ;
Kim, Yong Lim ;
Kim, Chan Duck ;
Shin, Gyu Tae ;
Yang, Chul Woo .
JOURNAL OF KOREAN MEDICAL SCIENCE, 2010, 25 (12) :1759-1765