A Population Dynamic Energy Budget-Based Tumor Growth Inhibition Model for Etoposide Effects on Wistar Rats.
Pharm Res
; 36(3): 38, 2019 Jan 11.
Article
em En
| MEDLINE
| ID: mdl-30635794
ABSTRACT
PURPOSE:
This work aimed to develop a population PK/PD tumor-in-host model able to describe etoposide effects on both tumor cells and host in Walker-256 tumor-bearing rats.METHODS:
Etoposide was investigated on thirty-eight Wistar rats randomized in five arms two groups of tumor-free animals receiving either placebo or etoposide (10 mg/kg bolus for 4 days) and three groups of tumor-bearing animals receiving either placebo or etoposide (5 or 10 mg/kg bolus for 8 or 4 days, respectively). To analyze experimental data, a tumor-in-host growth inhibition (TGI) model, based on the Dynamic Energy Budget (DEB) theory, was developed. Total plasma and free-interstitial tumor etoposide concentrations were assessed as driver of tumor kinetics.RESULTS:
The model simultaneously describes tumor and host growths, etoposide antitumor effect as well as cachexia phenomena related to both the tumor and the drug treatment. The schedule-dependent inhibitory effect of etoposide is also well captured when the intratumoral drug concentration is considered as the driver of the tumor kinetics.CONCLUSIONS:
The DEB-based TGI model capabilities, up to now assessed only in mice, are fully confirmed in this study involving rats. Results suggest that well designed experiments combined with a mechanistic modeling approach could be extremely useful to understand drug effects and to describe all the dynamics characterizing in vivo tumor growth studies.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Etoposídeo
/
Antineoplásicos Fitogênicos
Tipo de estudo:
Clinical_trials
/
Health_economic_evaluation
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália