Linked Life Data

19356106

Source:http://linkedlifedata.com/resource/pubmed/id/19356106

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-4-9
pubmed:abstractText
The serum concentration of valproic acid (VPA) in epilepsy patients decreased in the administration of carbapenem antibiotics (CP), such as meropenem, panipenem, biapenem or imipenem, to a sub-therapeutic level. The liver is the key organ for the decrease of VPA concentration by CP, because it has been reported that no decrease of the VPA level by CP was found in hepatectomized rats. This effect was also shown with monkey and rat liver slices. In this report, we show the results of in vitro inhibition of VPA-glucuronidase in human liver microsomes and cytosol by CP. We found the highest metabolic activity of VPA-glucuronide in human liver cytosol. The level in liver cytosol was 149 pmol/min/mg protein. The level in human liver microsomes (HLM) was one-fifth of that in cytosol and the level in serum was negligible. We found that this hydrolysis depends on VPA-glucuronidase in cytosol, because digestion was inhibited by D-saccharic acid 1,4-lactonemonohydrate of a specific inhibitor of beta-glucuronidase, but not by phenylmethylsulfonylfluoride of an esterase inhibitor. We also found the inhibition of VPA-glucuronidase in cytosol by CP, and the maximum inhibition was found with panipenem (IC(50) = 3 microM). We also found inhibition of VPA-glucuronidase in HLM by meropenem. These results showed that the inhibition in liver slices depended on the inhibition of VPA-glucuronidase by CP. We considered that the inhibition of VPA-glucuronidase by CP in cytosol is a key factor to decrease the plasma VPA level.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1872-3128
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
280-5
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Decreased valproate level caused by VPA-glucuronidase inhibition by carbapenem antibiotics.
pubmed:affiliation
Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
pubmed:publicationType
Journal Article