Linked Life Data

3396614

Source:http://linkedlifedata.com/resource/pubmed/id/3396614

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1988-9-8
pubmed:abstractText
The biotransformation of detomidine, a new alpha 2-adrenoceptor agonist, was studied using rat as the model animal. In vivo metabolism of the tritiated drug was compared to in vitro incubations with liver homogenates and intact, isolated hepatocytes. Metabolites were analysed by HPLC with radioactivity detection. The metabolic patterns in all systems were closely related. HPLC of urine gave twelve radioactive peaks. Tritiated water and unchanged 3H-detomidine were minor components. The two major peaks were tentatively identified as hydroxylated detomidine (14%) and its O-glucuronide (43%). Sulphate conjugates were not found. Isolated hepatocytes converted detomidine to the same two major products; the relative amount of the glucuronide increased with incubation time. In liver post-mitochondrial supernatant, hydroxylation was the dominant reaction, and the hydroxylated product comprised 74% of the total metabolites with non-induced and 50% with phenobarbital-induced liver. The major biotransformation in rat was thus concluded to be hydroxylation by the liver monooxygenases followed by glucuronic acid conjugation. The maximal rate of oxidation or the enzymatic capacity of a whole liver was estimated to be at least 100 nmol/min allowing for a high hepatic extraction ratio for detomidine. Together with the effective excretion of the glucuronide, this reaction sequence alone could account for the rapid elimination of the drug.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0378-7966
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
53-8
pubmed:dateRevised
2011-2-2
pubmed:meshHeading
pubmed:articleTitle
Metabolism of detomidine in the rat. I. Comparison of 3H-labelled metabolites formed in vitro and in vivo.
pubmed:affiliation
Farmos Group Ltd., Research Center, Turku, Finland.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro