Linked Life Data

12486679

Source:http://linkedlifedata.com/resource/pubmed/id/12486679

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-12-17
pubmed:abstractText
A population pharmacokinetic (PK) analysis was performed on plasma concentrations of GW468816 observed in dogs after 10, 25, and 50 mg/kg/day repeated intravenous administration. A two-compartment model was fitted to the concentration-time data using the NONMEM program. Dose and time dependency of PK parameters was investigated. Selection of the best model was performed using a stepwise approach. A Michaelis-Menten elimination process was used to describe the PK dose dependency, whereas an interoccasion variability on V(m) (the maximum elimination rate of the Michaelis-Menten elimination process) was initially used to describe the time dependency of the PKs, and the final model included an exponential function to account for time variance on V(m). The K(m) value of the final model was 29.6 microg/mL, whereas V(m) was estimated to vary with time from 4.97 microg/h/kg at day 1 to a maximum mean value of 9.64 microg/h/kg at day 14. This approach can be applied to either rich or sparse data leading to estimates of individual parameters by using Bayesian feedback. The overall information obtained can be used to interpret toxicological and pharmacological endpoints and integrated with further in vitro-in vivo studies to supply a comprehensive PK behavior before the first time in human studies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3549
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27-34
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
An application of nonlinear mixed-effects modeling to pharmacokinetic data exhibiting nonlinear and time-dependent behavior.
pubmed:affiliation
Clinical Pharmacokinetics/Modeling & Simulation, GlaxoSmithKline SpA, via Fleming 4, 37135, Verona, Italy. li14270@gsk.com
pubmed:publicationType
Journal Article