Clinical pharmacokinetics of mycophenolate mofetil in Japanese renal transplant recipients: A retrospective cohort study in a single center.
Mycophenolate mofetil (MMF), a morpholinoethyl ester of mycophenolic acid (MPA), is currently widely used in organ transplantation as an immunosuppressant. The usefulness of therapeutic drug monitoring (TDM) of MPA after MMF dosing is not clear in Japanese renal transplant patients. In this study, to obtain more information for TDM of MPA, the association between MPA pharmacokinetic characteristics and the development of the side effects, and the effect of other concomitant immunosupressants such as cyclospoline A (CyA), tacrolimus (FK) and predonisolone (PSL) on MPA pharmacokinetics were investigated in detail. Moreover, the effects of enterohepatic recirculation (EHRA) on pharmacokinetic characteristics of MPA and the development of the side effects were also investigated. AUC(MPA)(0-9) with FK medication was 1.3-1.9 times higher than that with CyA medication, and the contribution to the plasma level of MPA of FK might be smaller than that of CyA, because EHRA inhibition by CyA was 2 times greater than that by FK. AUC(MPA)(0-9) was not influenced by PSL. The association between AUC(MPA)(0-9) and the development of the side effects was not observed; however, the development of side effects (leukopenia and diarrhea) in the EHRA group was 2 times higher than that in the non-EHRA group. These results suggested that TDM for MPA after MMF dosing was desirable in Japanease transplant patients. However, though not frequently, AUC obtained by multiple blood sampling after MMF dosing was needed. In addition, EHRA has led to increasing interest in MMF medication.
Sugioka
Nobuyuki
N
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto, Japan. nsugioka@mb.kyoto-phu.ac.jp
Sasaki
Takayuki
T
Kokuhu
Takatoshi
T
Ito
Yukako
Y
Shibata
Nobuhito
N
Okamoto
Masahiko
M
Yoshimura
Norio
N
Takada
Kanji
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001798:Blood Proteins / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008102:Liver Circulation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011485:Protein Binding; D012189:Retrospective Studies
D001798:Blood Proteins; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid