Linked Life Data

12782943

Source:http://linkedlifedata.com/resource/pubmed/id/12782943

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-6-3
pubmed:abstractText
Our objective was to assess the distribution of paclitaxel in plasma and cerebrospinal fluid (CSF) in a cancer patient, and evaluate the role of the formulation vehicle Cremophor EL (CrEL) in drug distribution. Analysis of paclitaxel concentrations in CSF was performed using a triple-quadrupole mass spectrometric assay with electrospray ionization. Total and unbound paclitaxel levels in plasma were measured by liquid chromatography and equilibrium dialysis, respectively, and CrEL concentrations were determined by a colorimetric dye-binding microassay. Clinical samples were obtained from a 54-year-old female with breast cancer receiving a weekly regimen of paclitaxel (dose 60 mg/m2). The disposition of total paclitaxel in plasma was characterized by a bi-exponential elimination (terminal half-life 9.17 h) and a total clearance of 19.4 l/h/m2. The fraction of unbound paclitaxel in plasma ranged from 7.6 to 12.4% (unbound drug CL 176 l/h/m2). The plasma clearance of CrEL was 0.332 l/h/m2, whereas CrEL levels were undetectable in CSF (below 0.5 microl/ml). Concentrations of paclitaxel in CSF (range 45.5-162 pg/ml) and unbound CSF:unbound plasma concentration ratios (range 0.093-9.53%) progressively increased up to 24 h, with a mean unbound drug fraction in CSF of 84+/-3.6% (range 81-88%). These findings indicate that there is substantial distribution of paclitaxel to CSF. Since the fraction of unbound paclitaxel is different between plasma and CSF, measurement of unbound paclitaxel is required to accurately assess the extent of drug penetration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0959-4973
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
365-8
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Distribution of paclitaxel in plasma and cerebrospinal fluid.
pubmed:affiliation
Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
pubmed:publicationType
Journal Article, Clinical Trial