Linked Life Data

11269566

Source:http://linkedlifedata.com/resource/pubmed/id/11269566

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-3-27
pubmed:abstractText
Dichloroacetate (DCA) is a small molecule that reduces ambient concentrations of lactate in man. It was the purpose of this study to develop pharmacokinetic and pharmacodynamic models for determination of a dose for a pivotal Phase III clinical trial of DCA in patients with traumatic brain injury (TBI). Population pharmacokinetic and pharmacodynamic models were developed for DCA using NONMEM software. The pharmacokinetic data were fit to a physiologic two-compartment model, and the pharmacodynamic data were fit to an indirect physiologic response model. Simulations were employed to evaluate various dosing strategies for consideration in a pivotal Phase III clinical trial of DCA. For the pharmacokinetic model, it was discovered that the clearance of DCA decreased on multiple dosing from 4.82 L/h to 1.07 L/h and that the pharmacokinetics and pharmacodynamics in TBI patients could not be predicted from normal volunteers. Population pharmacokinetic modeling and simulation of the expected effects of several dosing strategies were useful procedures for designing a Phase III trial.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0091-2700
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
259-67
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Dichloroacetate: population pharmacokinetics with a pharmacodynamic sequential link model.
pubmed:affiliation
University of the Pacific, School of Pharmacy, Stockton, California, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study, Multicenter Study