Linked Life Data

12659422

Source:http://linkedlifedata.com/resource/pubmed/id/12659422

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-3-27
pubmed:abstractText
The purpose of this study was to develop a pharmacokinetic model simultaneously accounting for topotecan concentrations in plasma and saliva. Thirteen patients with metastatic epithelial ovarian cancer received topotecan. During the first and the second courses of treatment, each patient underwent pharmacokinetic evaluation. Data were analyzed using the nonlinear mixed-effect model program. The saliva concentrations were associated to a peripheral compartment while the central compartment described the plasma concentration time course. Thus, a three-compartment model was used; the basic parameters were: total clearance (CL), initial volume of distribution (V1), transfer rate constants (k12/k21 and k13/k31). The interoccasion variability was taken into account in the model. Data analysis was performed using a three-step approach; in step 2, a close relationship was found between creatinine CL and topotecan CL. The inclusion of this second stage model significantly improved the fit. Large interindividual variability in pharmacokinetic parameters occurred (CL varied from 10.4 to 23 L/h) while interoccasion variability was limited (6%). Seven additional courses were used for model validation. A limited sampling strategy using Bayesian estimation based on two sampling times (saliva at 25 min and plasma plus saliva at 8.5 h after the start of infusion) was developed. This study shows that salivary concentrations can be effectively used for drug monitoring.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0965-0407
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
211-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Modeling plasma and saliva topotecan concentration time course using a population approach.
pubmed:affiliation
Clinical Pharmacokinetic Laboratory, Faculty of Pharmacy, University Montpellier 1, 15 Avenue Ch. Flahault, BP 14 491, 34093 Montpellier Cedex 5, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't