Premium
The glucuronidation of mycophenolic acid by human liver, kidney and jejunum microsomes
Author(s) -
Bowalgaha Kushari,
Miners John O.
Publication year - 2001
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.0306-5251.2001.01487.x
Subject(s) - glucuronidation , microsome , jejunum , kidney , glucuronide , mycophenolic acid , medicine , chemistry , endocrinology , small intestine , metabolism , biochemistry , biology , in vitro , transplantation
Aims To estimate the relative contribution of liver, kidney and jejunum to MPA elimination via glucuronidation from in vitro kinetic data. Methods The kinetics of MPA glucuronidation by human liver, kidney and jejunum microsomes were characterized. Mycophenolic acid glucuronide (MPAG) concentrations in microsomal incubations were determined using a specific h.p.l.c. procedure. Non‐specific microsomal binding of MPA was excluded using an equilibrium dialysis approach. Results Microsomes from all three tissues catalysed the conversion of MPA to MPAG. Mean microsomal intrinsic clearances for MPAG formation by liver, kidney and jejunum microsomes were 46.6, 73.5 and 24.5 µl (min mg) −1 , respectively. When extrapolated to the whole organ, however, hepatic intrinsic clearance was 21‐ and 38‐fold higher than the respective intrinsic clearances for kidney and small intestine. Conclusions The data suggest that the liver is the organ primarily responsible for the systemic clearance of MPA, with little contribution from the kidney, and that the small intestine would be expected to contribute to first‐pass extraction to a minor extent only.