Linked Life Data

15585640

Source:http://linkedlifedata.com/resource/pubmed/id/15585640

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2004-12-8
pubmed:abstractText
In an era when molecular and targeted anticancer therapeutics is a major focus and when understanding drug dynamics in tumor is critical, it seems advantageous to be able to relate drug concentrations in tumors to corresponding biological end points. To that end, a novel method, based on physiologically based hybrid pharmacokinetic models, is presented to predict human tumor drug concentrations. Such models consist of a forcing function, describing the plasma drug concentration-time profile, which is linked to a model describing drug disposition in tumors. The hybrid models are originally derived from preclinical data and then scaled to humans. Integral to the scale-up procedure is the ability to derive human forcing functions directly from clinical pharmacokinetic data. Three examples of this approach are presented based on preclinical investigations with carboplatin, topotecan, and temozolomide. Translation of these preclinical hybrid models to humans used a Monte Carlo simulation technique that accounted for intrasubject and intersubject variability. Different pharmacokinetic end points, such as the AUC tumor, were extracted from the simulated human tumor drug concentrations to show how the predicted drug concentrations might be used to select drug-dosing regimens. It is believed that this modeling strategy can be used as an aid in the drug development process by providing key insights into drug disposition in tumors and by offering a foundation to optimize drug regimen design.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8048-58
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15585640-Animals, pubmed-meshheading:15585640-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:15585640-Brain Neoplasms, pubmed-meshheading:15585640-Carboplatin, pubmed-meshheading:15585640-Computer Simulation, pubmed-meshheading:15585640-Cyclohexanes, pubmed-meshheading:15585640-Dacarbazine, pubmed-meshheading:15585640-Female, pubmed-meshheading:15585640-Humans, pubmed-meshheading:15585640-Male, pubmed-meshheading:15585640-Models, Biological, pubmed-meshheading:15585640-Ovarian Neoplasms, pubmed-meshheading:15585640-Predictive Value of Tests, pubmed-meshheading:15585640-Rats, pubmed-meshheading:15585640-Rats, Inbred F344, pubmed-meshheading:15585640-Rats, Nude, pubmed-meshheading:15585640-Sesquiterpenes, pubmed-meshheading:15585640-Topotecan, pubmed-meshheading:15585640-Transplantation, Heterologous, pubmed-meshheading:15585640-Vascular Endothelial Growth Factor A
pubmed:year
2004
pubmed:articleTitle
Pharmacokinetic model-predicted anticancer drug concentrations in human tumors.
pubmed:affiliation
Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, PA 19140, USA. jmgallo@temple.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.