Linked Life Data

10955781

Source:http://linkedlifedata.com/resource/pubmed/id/10955781

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2000-11-27
pubmed:abstractText
The aim of this study was to investigate the clinical pharmacokinetics of 5-fluorouracil (5-FU) and its major metabolite 5-fluoro-5,6-dihydrouracil (5-FDHU) in 20 colorectal cancer patients given two dose levels of 5-FU, 250 and 370 mg/m2, administered by i.v. bolus. A reverse-phase high-performance liquid chromatographic method was used for the simultaneous assay of 5-FU and 5-FDHU in plasma samples obtained at baseline and at multiple time points from 5 min to 4 h after 5-FU bolus as well as to assess the activity of dihydropyrimidine dehydrogenase (DPD) in peripheral blood mononuclear cells (PBMCs) before 5-FU dosing. Plasma pharmacokinetic parameters of patients given 250 mg/m2 5-FU were significantly different from those receiving 370 mg/m2; main differences were observed in the trapezoidal areas under the plasma levels-versus-time curve from to to the last measurable concentration (area under the curve, 3.77+/-0.21 versus 13.61+/-2.3 h x microg/ml), peak plasma concentration (Cmax, 18.15+/-1.35 versus 48.41+/-7.69 microg/ml), and total body clearance (CL(TB), 54.64+/-3.54 versus 25.43+/-2.3 l/h/m2). Significant differences were also observed in the main pharmacokinetic parameters of 5-FDHU after 250 and 370 mg/m2 5-FU including the area under the curve from to to 4 h (5.39+/-0.32 versus 8.75+/-1.24 h x microg/ml), Cmax (3.60+/-0.16 versus 5.26+/-0.55 microg/ml) and time to Cmax (Tmax, 0.45+/-0.03 versus 0.69+/-0.06 h). The mean DPD activity in PBMCs in this group of patients was 205.7+/-36.4 pmol of 5-FDHU/min/mg of protein and was within the normal range; however, no significant correlations were found between 5-FU or 5-FDHU pharmacokinetic parameters at two dose levels and DPD activity of PBMCs. The results of the present study provide the first detailed comparison of the distribution of 5-FU and its major metabolite 5-FDHU at the therapeutic level as well as at reduced test dose levels to obtain pharmacokinetic data to be used as reference values for the identification of patients at risk of major 5-FU toxicity due to impaired metabolism to 5-FDHU.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3032-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Comparative pharmacokinetic analysis of 5-fluorouracil and its major metabolite 5-fluoro-5,6-dihydrouracil after conventional and reduced test dose in cancer patients.
pubmed:affiliation
Department of Oncology, Transplant and Advanced Technologies in Medicine, University of Pisa, Italy.
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study, Research Support, Non-U.S. Gov't