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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1999-2-10
|
| pubmed:abstractText |
Antitumor activity of topotecan, a new derivative of camptothecin, has been documented in many tumors. The active lactone form of topotecan is in equilibrium with the inactive hydroxyacid form. However, dose-limiting toxicity, neutropenia, is correlated to the area under the concentration time curve (AUC) of not only the lactone form but also total (lactone + hydroxyacid) topotecan. Because the determination of the total topotecan plasma concentration is technically much easier than the lactone, we sought to establish a limited sampling model for the AUC of total topotecan. Thirty-four pharmacokinetic profiles were obtained in 19 patients in a Phase I study of topotecan, which was infused over 30 min for 5 days. Multiple regression models predicting the AUC were developed using 17 profiles and validated using the rest of the data. The best model was: AUCpred (ng x h/ml) = 1.75 x C15m (ng/ml) + 11.2 x C6h (ng/ml) + 7.90 x dose (mg/m2), where AUCpred was the AUC predicted by the model, and C15m and C6h were the measured concentrations of total topotecan at 15 min and 6 h after the end of infusion, respectively. When this model was validated, it was unbiased (percentage of mean predicted error +/- SE, -1.0 +/- 3.3%) and precise (percentage of root mean square error, 11%). Because this model requires only two concentrations of total topotecan to estimate the AUC, it will be useful for further pharmacodynamic evaluation of topotecan in multi-institutional studies.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
1078-0432
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
2
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
43-6
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading | |
| pubmed:year |
1996
|
| pubmed:articleTitle |
Limited sampling model for area under the concentration time curve of total topotecan.
|
| pubmed:affiliation |
Department of Medicine, Committee on Clinical Pharmacology, and Cancer Research Center, University of Chicago, Chicago, Illinois 60637-1470, USA.
|
| pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Clinical Trial, Phase I
|