Linked Life Data

18215509

Source:http://linkedlifedata.com/resource/pubmed/id/18215509

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-3-24
pubmed:abstractText
We developed a pharmacokinetic/pharmacodynamic (PK/PD) mathematical model that fits voriconazole time-kill data against Candida isolates in vitro and used the model to simulate the expected kill curves for typical intravenous and oral dosing regimens. A series of Emax mathematical models were used to fit time-kill data for two isolates each of Candida albicans, Candida glabrata and Candida parapsilosis. PK parameters extracted from human data sets were used in the model to simulate kill curves for each isolate. Time-kill data were best fit by using an adapted sigmoidal Emax model that corrected for delays in candidal growth and the onset of voriconazole activity, saturation of the number of Candida and the steepness of the concentration-response curve. The rates of maximal killing by voriconazole (kmax) were highly correlated with the growth rates (ks) of the isolates (Pearson's correlation coefficient=0.9861). Simulations using PK parameters derived from the human data sets showed fungistatic effects against each of the isolates. In conclusion, we demonstrated that the activity of voriconazole against Candida isolates can be accurately described using a mathematical model. In the future, it might be possible to devise optimal dosing regimens of voriconazole using the model and PK data collected in vivo.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0924-8579
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
369-74
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
A pharmacokinetic/pharmacodynamic mathematical model accurately describes the activity of voriconazole against Candida spp. in vitro.
pubmed:affiliation
Department of Pharmaceutics, University of Florida College of Pharmacy, Gainesville, FL, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural