Mining Small Routine Clinical Data: A Population Pharmacokinetic Model and Optimal Sampling Times of Capecitabine and its Metabolites
Purpose: The present study was performed to demonstrate that small amounts of routine clinical data allow to generate valuable knowledge. Concretely, the aims of this research were to build a joint population pharmacokinetic model for capecitabine and three of its metabolites (5-DFUR, 5-FU and 5-FUH...
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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University of Alberta Libraries
2021
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| Online Access: | https://hdl.handle.net/10171/61900 |
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| author | Oyaga-Iriarte, E. (Esther) Insausti, A. (Asier) Bueno, L. (Lorea) Sayar, O. (Onintza) Aldaz, A. (Azucena) |
| author_facet | Oyaga-Iriarte, E. (Esther) Insausti, A. (Asier) Bueno, L. (Lorea) Sayar, O. (Onintza) Aldaz, A. (Azucena) |
| author_sort | Oyaga-Iriarte, E. (Esther) |
| collection | DSpace |
| description | Purpose: The present study was performed to demonstrate that small amounts of routine clinical data allow to generate valuable knowledge. Concretely, the aims of this research were to build a joint population pharmacokinetic model for capecitabine and three of its metabolites (5-DFUR, 5-FU and 5-FUH2) and to determine optimal sampling times for therapeutic drug monitoring.
Methods: We used data of 7 treatment cycles of capecitabine in patients with metastatic colorectal cancer. The population pharmacokinetic model was built as a multicompartmental model using NONMEM and was internally validated by visual predictive check. Optimal sampling times were estimated using PFIM 4.0 following D-optimality criterion.
Results: The final model was a multicompartmental model which represented the sequential transformations from capecitabine to its metabolites 5-DFUR, 5-FU and 5-FUH2 and was correctly validated. The optimal sampling times were 0.546, 0.892, 1.562, 4.736 and 8 hours after the administration of the drug. For its correct implementation in clinical practice, the values were rounded to 0.5, 1, 1.5, 5 and 8 hours after the administration of the drug.
Conclusions: Capecitabine, 5-DFUR, 5-FU and 5-FUH2 can be correctly described by the joint multicompartmental model presented in this work. The aforementioned times are optimal to maximize the information of samples. Useful knowledge can be obtained for clinical practice from small databases. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-61900 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2021 |
| publisher | University of Alberta Libraries |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-619002021-09-03T01:05:40Z Mining Small Routine Clinical Data: A Population Pharmacokinetic Model and Optimal Sampling Times of Capecitabine and its Metabolites Oyaga-Iriarte, E. (Esther) Insausti, A. (Asier) Bueno, L. (Lorea) Sayar, O. (Onintza) Aldaz, A. (Azucena) Materias Investigacion::Ciencias de la Salud::Química médica Therapeutic drug monitoring Capecitabine Metabolites Pharmacokinetic model Purpose: The present study was performed to demonstrate that small amounts of routine clinical data allow to generate valuable knowledge. Concretely, the aims of this research were to build a joint population pharmacokinetic model for capecitabine and three of its metabolites (5-DFUR, 5-FU and 5-FUH2) and to determine optimal sampling times for therapeutic drug monitoring. Methods: We used data of 7 treatment cycles of capecitabine in patients with metastatic colorectal cancer. The population pharmacokinetic model was built as a multicompartmental model using NONMEM and was internally validated by visual predictive check. Optimal sampling times were estimated using PFIM 4.0 following D-optimality criterion. Results: The final model was a multicompartmental model which represented the sequential transformations from capecitabine to its metabolites 5-DFUR, 5-FU and 5-FUH2 and was correctly validated. The optimal sampling times were 0.546, 0.892, 1.562, 4.736 and 8 hours after the administration of the drug. For its correct implementation in clinical practice, the values were rounded to 0.5, 1, 1.5, 5 and 8 hours after the administration of the drug. Conclusions: Capecitabine, 5-DFUR, 5-FU and 5-FUH2 can be correctly described by the joint multicompartmental model presented in this work. The aforementioned times are optimal to maximize the information of samples. Useful knowledge can be obtained for clinical practice from small databases. 2021-09-02T06:57:24Z 2021-09-02T06:57:24Z 2019 info:eu-repo/semantics/article https://hdl.handle.net/10171/61900 eng 10.18433/jpps30392 info:eu-repo/semantics/openAccess application/pdf University of Alberta Libraries |
| spellingShingle | Materias Investigacion::Ciencias de la Salud::Química médica Therapeutic drug monitoring Capecitabine Metabolites Pharmacokinetic model Oyaga-Iriarte, E. (Esther) Insausti, A. (Asier) Bueno, L. (Lorea) Sayar, O. (Onintza) Aldaz, A. (Azucena) Mining Small Routine Clinical Data: A Population Pharmacokinetic Model and Optimal Sampling Times of Capecitabine and its Metabolites |
| title | Mining Small Routine Clinical Data: A Population Pharmacokinetic Model and Optimal Sampling Times of Capecitabine and its Metabolites |
| title_full | Mining Small Routine Clinical Data: A Population Pharmacokinetic Model and Optimal Sampling Times of Capecitabine and its Metabolites |
| title_fullStr | Mining Small Routine Clinical Data: A Population Pharmacokinetic Model and Optimal Sampling Times of Capecitabine and its Metabolites |
| title_full_unstemmed | Mining Small Routine Clinical Data: A Population Pharmacokinetic Model and Optimal Sampling Times of Capecitabine and its Metabolites |
| title_short | Mining Small Routine Clinical Data: A Population Pharmacokinetic Model and Optimal Sampling Times of Capecitabine and its Metabolites |
| title_sort | mining small routine clinical data: a population pharmacokinetic model and optimal sampling times of capecitabine and its metabolites |
| topic | Materias Investigacion::Ciencias de la Salud::Química médica Therapeutic drug monitoring Capecitabine Metabolites Pharmacokinetic model |
| url | https://hdl.handle.net/10171/61900 |
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