Abstract | BACKGROUND: OBJECTIVES: The aim of this study was to develop a pharmacokinetic-pharmacodynamic model to predict the distribution of tamoxifen and endoxifen quantitatively, and to discover the anti- tumor effect patterns of tamoxifen and endoxifen. METHODS: The pharmacokinetic-pharmacodynamic model was established by integrating a four compartments pharmacokinetics model and a pharmacodynamic model, the first one include central compartment and peripheral compartment both of which contain tamoxifen and endoxifen. The parameters of the model were calculated by the values of plasma concentrations and the tumor growth data before and after the administration of tamoxifen. RESULTS: The transport rate k42 (6.0003) of endoxifen from the peripheral compartment to the central compartment and the metabolism rate k34 (0.0031) from tamoxifen to endoxifen in the peripheral compartment were proven to be significant, which showed that tamoxifen and endoxifen are mainly distributed in the central compartment. The model provided reasonable predictions of tumor growth, which was inhibited after the administration and varies with the concentration of endoxifen. CONCLUSION: We established a PK-PD model of tamoxifen and endoxifen to predict the tumor growth. The parameters of the pharmacodynamic model, which characterized the tumor growth, revealed the patterns of tamoxifen's anti- tumor functions. The PK-PD model successfully provided illustration for the pharmacokinetics of tamoxifen and endoxifen, and predicted the inhibition effect of endoxifen on the tumor growth.
|
Authors | Shengyue Yuan, Qingrong Sun, Yao Chen, Jun Liao |
Journal | Drug metabolism letters
(Drug Metab Lett)
Vol. 11
Issue 2
Pg. 93-101
( 2017)
ISSN: 1874-0758 [Electronic] United Arab Emirates |
PMID | 28814243
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright© Bentham Science Publishers; For any queries, please email at [email protected]. |
Chemical References |
- Antineoplastic Agents, Hormonal
- Tamoxifen
- 4-hydroxy-N-desmethyltamoxifen
|
Topics |
- Antineoplastic Agents, Hormonal
(pharmacology, therapeutic use)
- Breast Neoplasms
(drug therapy)
- Female
- Humans
- Models, Biological
- Tamoxifen
(analogs & derivatives, pharmacology, therapeutic use)
|