Linked Life Data

21246315

Source:http://linkedlifedata.com/resource/pubmed/id/21246315

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-2-2
pubmed:abstractText
Progress in an understanding of the genetic basis of cancer coupled to molecular pharmacology of potential new anticancer drugs calls for new approaches that are able to address key issues in the drug development process, including pharmacokinetic (PK) and pharmacodynamic (PD) relationships. The incorporation of predictive preclinical PK/PD models into rationally designed early-stage clinical trials offers a promising way to relieve a significant bottleneck in the drug discovery pipeline. The aim of the current review is to discuss some considerations for how quantitative PK and PD analyses for anticancer drugs may be conducted and integrated into a global translational effort, and the importance of examining drug disposition and dynamics in target tissues to support the development of preclinical PK/PD models that can be subsequently extrapolated to predict pharmacologic characteristics in patients. In this article, we describe three different physiologically based (PB) PK modeling approaches, i.e., the whole-body PBPK model, the hybrid PBPK model, and the two-pore model for macromolecules, as well as their applications. General conclusions are that greater effort should be made to generate more clinical data that could validate scaled preclinical PB-PK/PD tumor-based models and, thus, stimulate a framework for preclinical to clinical translation. Finally, given the innovative techniques to measure tissue drug concentrations and associated biomarkers of drug responses, development of predictive PK/PD models will become a standard approach for drug discovery and development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1550-7416
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
111-20
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The pharmacokinetic/pharmacodynamic pipeline: translating anticancer drug pharmacology to the clinic.
pubmed:affiliation
Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York 10029, USA.
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Extramural