Linked Life Data

15283300

Source:http://linkedlifedata.com/resource/pubmed/id/15283300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2004-7-30
pubmed:abstractText
The pharmacokinetics and metabolism of the antioxidant and reactive oxygen scavenger alpha-phenyl-N-tert-butyl nitrone (PBN) was examined in the male cynomolgus monkey after intravenous administration. Following an i.v. bolus dose of 5 mg/kg, plasma concentrations of PBN declined in a bi-exponential fashion. PBN demonstrated a moderate plasma clearance (CL(p) = 27.02 +/- 6.46 ml/min/kg) and a moderate volume of distribution at steady state (Vd(ss) = 1.70 +/- 0.23 l/kg), resulting in a terminal elimination half-life of 0.76 +/- 0.25 h. The corresponding area under the curve (AUC(0-infinity)) was 3.20 +/- 0.77 microg-h/ml. Scale-up of the in vitro microsomal intrinsic clearance data for PBN afforded a blood clearance (CLb) value of 22 ml/min/kg, which was in reasonable agreement with the observed in vivo CLb. Monkey liver microsomes catalyzed the NADPH-dependent monohydroxylation of PBN to the corresponding alpha-4-hydroxyphenyl-N-tert-butylnitrone (4-HOPBN) metabolite. The formation of 4-HOPBN and its corresponding O-glucuronide was also discernible upon qualitative analysis of pooled (0-24 h) monkey plasma and urine samples. Less than 5% of the administered dose was excreted as unchanged PBN in the urine, suggesting that P450-catalyzed metabolism constituted the major route of PBN clearance in the primate. In conclusion, the pharmacokinetic attributes and the clearance mechanism of PBN in the cynomolgus monkey is similar to that observed in the Sprague-Dawley rat.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0792-5077
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11-24
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Intravenous pharmacokinetics and metabolism of the reactive oxygen scavenger alpha-phenyl-N-tert-butyl nitrone (PBN) in the cynomolgus monkey.
pubmed:affiliation
Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research & Development, Groton, CT 06340, USA.
pubmed:publicationType
Journal Article, Comparative Study