A semi-physiological-based pharmacokinetic/pharmacodynamic model to describe the effects of topotecan on b-lymphocyte lineage cells.
Pharm Res
; 27(3): 431-41, 2010 Mar.
Article
en En
| MEDLINE
| ID: mdl-20101520
ABSTRACT
PURPOSE:
To develop a semi-physiological-based model describing simultaneously the time course of immature and mature B-lymphocytes after topotecan (TPT) administration to tumor-bearing rats.METHODS:
Twenty-four tumor-bearing BDIX male rats received a single 6 mg/kg intra-peritoneal dose of TPT or saline. Mature and immature B-cell levels were measured every two days during three weeks and showed a very different temporal pattern. Both B-cell populations declined rapidly, reaching the nadir at 3-4 days after TPT administration; however, mature cells returned to baseline at day 8, while immature B-cells stayed at nadir until day 9 instead. Data were modeled using the population approach with NONMEM VI.RESULTS:
The model developed maintains the proliferation, maturation and degradation elements of previous published models for myelosuppresion. In order to describe the rapid recovery of mature cells, it includes a peripheral compartment providing a constant supply of mature cells to the bloodstream.CONCLUSIONS:
The major contribution of the model is its new structure and the dynamical consequences, demonstrating an independent behavior between mature and immature B-cells during recovery. The final model could represent a good basis for the optimization of cytotoxic drugs oriented to attain a maximum antitumor efficacy while minimizing hematological toxicity.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Topotecan
/
Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Pharm Res
Año:
2010
Tipo del documento:
Article
País de afiliación:
España