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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1995-6-8
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pubmed:abstractText |
The objective of this study was to develop a limited sampling model (LSM) to estimate the area under the curve (AUC) of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and that of 7-ethyl-10-hydroxycamptothecin (SN-38) as predictive pharmacokinetic variables for leukopenia and episodes of diarrhea induced by CPT-11 administration. The model was developed with a training set consisting of pharmacokinetic studies in 36 patients who received a 90-min i.v. infusion of CPT-11 at a dose of 100 mg/m2. A multiple regression analysis of CPT-11 or SN-38 concentrations observed at each time point in the training set was used to predict the AUC of CPT-11 or SN-38. The final sampling models using only two time points were: AUCCPT-11 = 3.7891*C2.5 + 14.0479*C13.5 + 1.5463 AUCSN-38 = 0.5319*C2.5 + 19.1468*C13.5 + 72.7349 where C2.5 and C13.5 are the plasma concentration of CPT-11 (micrograms/ml) or SN-38 (ng/ml) at 2.5 and 13.5 h after the initiation of CPT-11 infusion, respectively. The models were validated prospectively on a separate test data set of 12 patients receiving the same dose of CPT-11 investigated in a previous study. Validation of the final LSM on the test data set gave values of root mean square error (RMSE) of 12.72% and 5.97% for the AUC of CPT-11 and that of SN-38, respectively. The model can be used to monitor the AUCs of both CPT-11 and SN-38 for the early prediction of toxicities and to establish a pharmacokinetically based dose modification strategy for safe administration of CPT-11.
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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:month |
Jan
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pubmed:issn |
0910-5050
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
86
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
117-23
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pubmed:dateRevised |
2007-9-25
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pubmed:meshHeading |
pubmed-meshheading:7737903-Adult,
pubmed-meshheading:7737903-Aged,
pubmed-meshheading:7737903-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:7737903-Blood Specimen Collection,
pubmed-meshheading:7737903-Camptothecin,
pubmed-meshheading:7737903-Female,
pubmed-meshheading:7737903-Humans,
pubmed-meshheading:7737903-Male,
pubmed-meshheading:7737903-Middle Aged,
pubmed-meshheading:7737903-Models, Biological,
pubmed-meshheading:7737903-Prospective Studies,
pubmed-meshheading:7737903-Regression Analysis
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pubmed:year |
1995
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pubmed:articleTitle |
A limited sampling model for estimating pharmacokinetics of CPT-11 and its metabolite SN-38.
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pubmed:affiliation |
Department of Medicine, National Cancer Center Hospital East, Chiba.
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, Non-U.S. Gov't
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