IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide
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IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide.
Inosine 5'-monophosphate dehydrogenase (IMP-DH) activities were measured in human lymphocytes (exhibiting type I IMP-DH activity) and human lymphoblasts (exhibiting type II IMP-DH activity) in the presence of various amounts of mycophenolic acid (MPA) (0-20 mumol/L) and MPA glucuronide (MPAG) (0-200 mumol/L). Moreover, the influences of human serum albumin (HSA) and human plasma on the MPA- and...
متن کاملPharmacodynamic assessment of mycophenolic acid-induced immunosuppression by measuring IMP dehydrogenase activity.
Pharmacodynamic monitoring of the biological effect of immunosuppressive drugs provides an alternative to traditional therapeutic drug monitoring. We chose this method to investigate mycophenolic acid (MPA), an immunosuppressive drug that mediates its effect by inhibition of IMP dehydrogenase (IMPDH), a key enzyme in the de novo biosynthesis of purines. Using an assay developed for measuring IM...
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1. Mycophenolic acid, an antibiotic of some antiquity that more recently has been found to have marked activity against a range of tumours in mice and rats, strongly inhibits DNA synthesis in the L strain of fibroblasts in vitro. 2. The extent of the inhibition of DNA synthesis is markedly increased by preincubation of the cells with mycophenolic acid before the addition of [(14)C]thymidine. 3....
متن کاملDetermination of the acyl glucuronide metabolite of mycophenolic acid in human plasma by HPLC and Emit.
BACKGROUND The acyl glucuronide (AcMPAG) of mycophenolic acid (MPA) has been found to possess pharmacologic and potentially proinflammatory activity in vitro. To establish its pharmacologic and toxicologic relevance in vivo, a reversed-phase HPLC method was modified to simultaneously determine MPA, the phenolic MPA-glucuronide (7-O-MPAG), and AcMPAG. In addition, cross-reactivity of AcMPAG in t...
متن کاملQuantification of mycophenolic acid and glucuronide metabolite in human serum by HPLC-tandem mass spectrometry.
BACKGROUND The potent immunosuppressant mycophenolic acid (MPA) is metabolized to an inactive glucuronide (MPAG). The extent of metabolism varies among individuals, and the MPAG formed can be hydrolyzed to MPA and can displace MPA from serum albumin, creating a potential need to monitor both MPA and MPAG. METHODS After addition of the carboxybutoxy ether of MPA (MPAC) as internal standard, MP...
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ژورنال
عنوان ژورنال: Clinical Chemistry
سال: 1997
ISSN: 0009-9147,1530-8561
DOI: 10.1093/clinchem/43.12.2312