Journal article
Comparative metabolism of mycophenolic acid by glucuronic acid and glucose conjugation in human, dog, and cat liver microsomes
Journal of veterinary pharmacology and therapeutics, Vol.40(2), pp.123-129
04/2017
Handle:
https://hdl.handle.net/2376/106109
PMCID: PMC5159325
PMID: 27301298
Abstract
Use of the immunosuppressant mycophenolic acid (MPA) in cats is limited because MPA elimination depends on glucuronidation, which is deficient in cats. We evaluated formation of major (phenol glucuronide) and minor (acyl glucuronide, phenol glucoside, and acyl glucoside) MPA metabolites using liver microsomes from 16 cats, 26 dogs, and 48 humans. All MPA metabolites were formed by human liver microsomes, while dog and cat liver microsomes formed both MPA glucuronides, but only one MPA glucoside (phenol glucoside). Intrinsic clearance (CLint) of MPA for phenol glucuronidation by cat liver microsomes was only 15-17% that of dog and human liver microsomes. However, CLint for acyl glucuronide and phenol glucoside formation in cat liver microsomes was similar to or greater than that for dog and human liver microsomes. While total MPA conjugation CLint was generally similar for cat liver microsomes compared with dog and human liver microsomes, relative contributions of each pathway varied between species with phenol glucuronidation predominating in dog and human liver microsomes and phenol glucosidation predominating in cat liver microsomes. MPA conjugation variation between cat liver microsomes was threefold for total conjugation and for phenol glucosidation, sixfold for phenol glucuronidation, and 11-fold for acyl glucuronidation. Our results indicate that total MPA conjugation is quantitatively similar between liver microsomes from cats, dogs, and humans despite large differences in the conjugation pathways that are utilized by these species.
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Details
- Title
- Comparative metabolism of mycophenolic acid by glucuronic acid and glucose conjugation in human, dog, and cat liver microsomes
- Creators
- J E Slovak - Department of Veterinary Clinical Sciences, Program in Individualized Medicine, Washington State University, Pullman, WA, USAK Mealey - Department of Veterinary Clinical Sciences, Program in Individualized Medicine, Washington State University, Pullman, WA, USAM H Court - Department of Veterinary Clinical Sciences, Program in Individualized Medicine, Washington State University, Pullman, WA, USA
- Publication Details
- Journal of veterinary pharmacology and therapeutics, Vol.40(2), pp.123-129
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Publisher
- England
- Grant note
- R01 GM102130 / NIGMS NIH HHS
- Identifiers
- 99900546981401842
- Language
- English
- Resource Type
- Journal article