Linked Life Data

16200545

Source:http://linkedlifedata.com/resource/pubmed/id/16200545

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-10-6
pubmed:abstractText
Many naturally occurring and synthetic isothiocyanates can inhibit chemical carcinogenesis in animal models. Recently, we found that alpha-naphthyl isothiocyanate (1-NITC) inhibited P-glycoprotein- and multidrug resistance associated protein 1-mediated efflux, indicating the potential application of 1-NITC as a chemosensitizing agent for cancer chemotherapy. The objective of this study was to explore the pharmacokinetic characteristics of 1-NITC in rats. A single dose of 10, 25, 50, or 75 mg/kg of 1-NITC was administered intravenously or orally to female Sprague-Dawley rats (n = 4 for each group). Dose-normalized concentration-time profiles were not superimposable following intravenous or oral dosing, indicating that the disposition of 1-NITC in rats was nonlinear. As doses increased from 10 to 75 mg/kg following iv administration, the total clearance decreased from 2.2 +/- 0.9 to 0.8 +/- 0.3 L/h/kg; oral availability averaged 0.46 for oral doses of 10-75 mg/kg. A nonlinear two-compartment open model with capacity-limited absorption and capacity-limited elimination from the central compartment best fit the data, based on goodness-of-fit criteria. The mechanism underlying the nonlinear elimination of 1-NITC in rats is most likely due to the capacity-limited metabolism of 1-NITC. This study represents the first report of the pharmacokinetics of 1-NITC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3549
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2441-51
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Pharmacokinetics of alpha-naphthyl isothiocyanate in rats.
pubmed:affiliation
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, New York 14260, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't