Source:http://linkedlifedata.com/resource/pubmed/id/10389915
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
1999-9-30
|
| pubmed:abstractText |
A novel derivative of camptothecin, 9-aminocamptothecin (9-AC), is currently under Phase II evaluation in various cancers. Exceptionally mild toxicities were observed in patients with brain tumors who were treated with anticonvulsants. To investigate a pharmacokinetic interaction between 9-AC and anticonvulsants, and to evaluate the pharmacodynamics of 9-AC, we investigated the clinical pharmacology of 9-AC, administered by a 72-h infusion, in three Phase II studies. Plasma concentrations of total 9-AC (lactone plus carboxylate) at a steady state were measured in 56, 10, and 14 patients with non-small cell lung cancer, malignant glioma, and head and neck cancer, respectively. For lung cancer or glioma patients, 9-AC was infused at 45 (51 patients) or 59 (15 patients) microg/m2/h, and 9-AC was infused at 35.4 microg/m2/h in head and neck cancer patients. All glioma patients had been treated with phenytoin or carbamazepine. 9-AC clearance did not differ among the dosage rates, but differed according to the diseases (P = 0.002). Glioma patients had a higher clearance (1.0-18.0; median, 2.0 liters/h/m2) than lung cancer patients (0.3-5.1; median, 0.9 liters/h/m2). A logistic regression model described the relationship between the 9-AC concentration and the probability of grade 4 neutropenia, which was the main toxicity. Observed incidences of grade 4 neutropenia for patients with model-predicted probability of 0-20%, 20-40%, and 40-100% were 10%, 32%, and 67%, respectively, and corresponded to 9-AC concentration of <54, 54-86, and >86 ng/ml, respectively. Anticonvulsants seem to induce the clearance of 9-AC, and the concentration of 9-AC predicts the probability of grade 4 neutropenia.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
1078-0432
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
5
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1325-30
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| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:10389915-Adult,
pubmed-meshheading:10389915-Aged,
pubmed-meshheading:10389915-Anticonvulsants,
pubmed-meshheading:10389915-Blood Cell Count,
pubmed-meshheading:10389915-Brain Neoplasms,
pubmed-meshheading:10389915-Camptothecin,
pubmed-meshheading:10389915-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:10389915-Carcinoma, Squamous Cell,
pubmed-meshheading:10389915-Drug Administration Schedule,
pubmed-meshheading:10389915-Female,
pubmed-meshheading:10389915-Glioma,
pubmed-meshheading:10389915-Granulocyte Colony-Stimulating Factor,
pubmed-meshheading:10389915-Head and Neck Neoplasms,
pubmed-meshheading:10389915-Humans,
pubmed-meshheading:10389915-Infusions, Intravenous,
pubmed-meshheading:10389915-Logistic Models,
pubmed-meshheading:10389915-Lung Neoplasms,
pubmed-meshheading:10389915-Male,
pubmed-meshheading:10389915-Metabolic Clearance Rate,
pubmed-meshheading:10389915-Middle Aged
|
| pubmed:year |
1999
|
| pubmed:articleTitle |
Pharmacokinetics and pharmacodynamics of 9-aminocamptothecin infused over 72 hours in phase II studies.
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| pubmed:affiliation |
Section of Hematology/Oncology, The University of Chicago, Illinois 60637, USA.
|
| pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Multicenter Study,
Clinical Trial, Phase II
|