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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2-3
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pubmed:dateCreated |
1994-1-24
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pubmed:abstractText |
We have investigated the pharmacokinetics of the investigational semi-synthetic vinca alkaloid vinorelbine (navelbine, NVB). The analyses have been performed by using a sensitive and selective method based on ion-exchange normal phase high-performance liquid chromatography with fluorescence detection combined with liquid-liquid extraction for sample clean-up. Pharmacokinetic studies were performed in male FVB mice receiving 12 mg/kg NVB through intravenous injection. The results have been compared to those obtained for vinblastine (VBL). The plasma pharmacokinetics of NVB can be described by a three compartment model. The elimination half-life is significantly longer and the plasma AUC values higher for NVB compared to VBL. This is reflected in tissues, where, 24 hr after drug administration, the concentration of NVB is 5 to 10-fold higher compared to VBL. Qualitatively, the tissue distribution and retention of the drugs is very similar. The drug concentrations in most tissues decline parallel with the circulating plasma levels, whereas prolonged retention is found in tissues of lymphatic and testicular origin. Deacetylation yielding deacetylnavelbine (DNVB) is the primary metabolic route for NVB. This cytotoxic metabolite accounts for a substantial part of the overall disposition of drug. Only 58% of the administered dose is excreted in the urine (17%) and faeces (41%) as NVB or DNVB. No other metabolites have been detected.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
0167-6997
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
141-50
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:8262726-Animals,
pubmed-meshheading:8262726-Antineoplastic Agents,
pubmed-meshheading:8262726-Chromatography, High Pressure Liquid,
pubmed-meshheading:8262726-Feces,
pubmed-meshheading:8262726-Leukemia L1210,
pubmed-meshheading:8262726-Male,
pubmed-meshheading:8262726-Mice,
pubmed-meshheading:8262726-Mice, Inbred Strains,
pubmed-meshheading:8262726-Reproducibility of Results,
pubmed-meshheading:8262726-Sensitivity and Specificity,
pubmed-meshheading:8262726-Tissue Distribution,
pubmed-meshheading:8262726-Tumor Cells, Cultured,
pubmed-meshheading:8262726-Vinblastine
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pubmed:articleTitle |
Plasma pharmacokinetics, tissue disposition, excretion and metabolism of vinorelbine in mice as determined by high performance liquid chromatography.
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pubmed:affiliation |
Department of Clinical Chemistry, Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, Amsterdam.
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pubmed:publicationType |
Journal Article
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