A Mathematical Model for Cisplatin Cellular Pharmacodynamics
A simple theoretical model for the cellular pharmacodynamics of cisplatin is presented. The model, which takes into account the kinetics of cisplatin uptake by cells and the intracellular binding of the drug, can be used to predict the dependence of survival (relative to controls) on the time course...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2003-03-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558603800088 |
| _version_ | 1818277342493016064 |
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| author | Ardith W. El-Kareh Timothy W. Secomb |
| author_facet | Ardith W. El-Kareh Timothy W. Secomb |
| author_sort | Ardith W. El-Kareh |
| collection | DOAJ |
| description | A simple theoretical model for the cellular pharmacodynamics of cisplatin is presented. The model, which takes into account the kinetics of cisplatin uptake by cells and the intracellular binding of the drug, can be used to predict the dependence of survival (relative to controls) on the time course of extracellular exposure. Cellular pharmacokinetic parameters are derived from uptake data for human ovarian and head and neck cancer cell lines. Survival relative to controls is assumed to depend on the peak concentration of DNA-bound intracellular platinum. Model predictions agree well with published data on cisplatin cytotoxicity for three different cancer cell lines, over a wide range of exposure times. In comparison with previously published mathematical models for anticancer drug pharmacodynamics, the present model provides a better fit to experimental data sets including long exposure times (∼100 hours). The model provides a possible explanation for the fact that cell kill correlates well with area under the extracellular concentration-time curve in some data sets, but not in others. The model may be useful for optimizing delivery schedules and for the dosing of cisplatin for cancer therapy. |
| first_indexed | 2024-12-12T23:00:01Z |
| format | Article |
| id | doaj.art-1a6e1daf09924a87b5db1e2c24b2cdbb |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-12T23:00:01Z |
| publishDate | 2003-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-1a6e1daf09924a87b5db1e2c24b2cdbb2022-12-22T00:08:50ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022003-03-015216116910.1016/S1476-5586(03)80008-8A Mathematical Model for Cisplatin Cellular PharmacodynamicsArdith W. El-Kareh0Timothy W. Secomb1ARL-Microcirculation Division, University of Arizona, Tucson, AZ 85724-5051, USADepartment of Physiology, University of Arizona, Tucson, AZ 85724-5051, USAA simple theoretical model for the cellular pharmacodynamics of cisplatin is presented. The model, which takes into account the kinetics of cisplatin uptake by cells and the intracellular binding of the drug, can be used to predict the dependence of survival (relative to controls) on the time course of extracellular exposure. Cellular pharmacokinetic parameters are derived from uptake data for human ovarian and head and neck cancer cell lines. Survival relative to controls is assumed to depend on the peak concentration of DNA-bound intracellular platinum. Model predictions agree well with published data on cisplatin cytotoxicity for three different cancer cell lines, over a wide range of exposure times. In comparison with previously published mathematical models for anticancer drug pharmacodynamics, the present model provides a better fit to experimental data sets including long exposure times (∼100 hours). The model provides a possible explanation for the fact that cell kill correlates well with area under the extracellular concentration-time curve in some data sets, but not in others. The model may be useful for optimizing delivery schedules and for the dosing of cisplatin for cancer therapy.http://www.sciencedirect.com/science/article/pii/S1476558603800088chemotherapycellular pharmacodynamicscisplatincellular pharmacokineticsarea under the curve |
| spellingShingle | Ardith W. El-Kareh Timothy W. Secomb A Mathematical Model for Cisplatin Cellular Pharmacodynamics Neoplasia: An International Journal for Oncology Research chemotherapy cellular pharmacodynamics cisplatin cellular pharmacokinetics area under the curve |
| title | A Mathematical Model for Cisplatin Cellular Pharmacodynamics |
| title_full | A Mathematical Model for Cisplatin Cellular Pharmacodynamics |
| title_fullStr | A Mathematical Model for Cisplatin Cellular Pharmacodynamics |
| title_full_unstemmed | A Mathematical Model for Cisplatin Cellular Pharmacodynamics |
| title_short | A Mathematical Model for Cisplatin Cellular Pharmacodynamics |
| title_sort | mathematical model for cisplatin cellular pharmacodynamics |
| topic | chemotherapy cellular pharmacodynamics cisplatin cellular pharmacokinetics area under the curve |
| url | http://www.sciencedirect.com/science/article/pii/S1476558603800088 |
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