Linked Life Data

10416266

Source:http://linkedlifedata.com/resource/pubmed/id/10416266

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-10-13
pubmed:abstractText
The derivation of the optimal design for an upcoming toxicokinetic study of butadiene in humans is presented. The specific goal of the planned study is to obtain a precise estimate of butadiene metabolic clearance for each study subject, together with a good characterization of its population variance. We used a two-compartment toxicokinetic model, imbedded in a hierarchical population model of variability, in conjunction with a preliminary set of butadiene kinetic data in humans, as a basis for design optimization. Optimization was performed using Monte Carlo simulations. Candidate designs differed in the number and timing of exhaled air samples to be collected. Simulations indicated that only 10 air samples should be necessary to obtain a coefficient of variation of 15% for the estimated clearance rate, if the timing of those samples is properly chosen. Optimal sampling times were found to closely bracket the end of exposure. This efficient design will allow the recruitment of more subjects in the study, in particular to match prescribed levels of accuracy in the estimate of the population variance of the butadiene metabolic rate constant. The techniques presented here have general applicability to the design of human and animal toxicology studies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
213-24
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Optimal design for a study of butadiene toxicokinetics in humans.
pubmed:affiliation
Lawrence Berkeley National Laboratory, California, USA. fbois@diana.lbl.gov
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't