Linked Life Data

2731406

Source:http://linkedlifedata.com/resource/pubmed/id/2731406

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1989-7-25
pubmed:abstractText
The disposition and elimination kinetics of the enantiomers of E-10-hydroxynortriptyline (E-10-OH-NT) were studied in six rapid and four slow hydroxylators of debrisoquin after a single oral dose of 75 mg racemic E-10-OH-NT hydrogen maleate. The plasma levels and the AUC of unconjugated (-)E-10-OH-NT were two to five times higher than those of (+)E-10-OH-NT. The plasma half-lives of both enantiomers were 8 to 9 hours. A significantly higher proportion of the given dose of (+)E-10-OH-NT (64.4% +/- 12.1%) than of (-)E-10-OH-NT (35.3% +/- 9.7%) was recovered in urine as glucuronide conjugate, but more (-)E-10-OH-NT was recovered unchanged in urine. The total oral plasma clearance and the metabolic clearance by glucuronidation were significantly (p less than 0.0001) higher for (+)E-10-OH-NT than for (-)E-10-OH-NT. The findings indicate that first-pass glucuronidation of E-10-OH-NT is enantioselective in human beings in vivo, with preference for (+)E-10-OH-NT. The renal clearance of unbound (-)E-10-OH-NT (0.57 +/- 0.16 L.kg-1.hr-1), on the other hand, exceeded that of (+)E-10-OH-NT (0.44 +/- 0.14 L.kg-1.hr-1) (p less than 0.005), which suggests enantioselective tubular secretion. The debrisoquin hydroxylation status was not associated with any of the investigated kinetic processes that relate to E-10-OH-NT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0009-9236
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
650-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Stereoselective disposition of racemic E-10-hydroxynortriptyline in human beings.
pubmed:affiliation
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't