Articulo
Relationship between lactone ratios of 9-nitrocamptothecin and their lactone/carboxylate equilibria in vitro and in vivo
Registro en:
issn:0326-2383
Autor
Chen, Jun
Hu, Rongrong
Yang, Xixiong
Tian, Rong
Gu, Wei
Chen, Zhipeng
Cai, Baochang
Institución
Resumen
The aim of this study was to evaluate the effect of lactone ratios on the lactone/carboxylate equilibria of 9-nitrocamptothecin (9-NC) in vitro and in vivo. The interconversion of lactone and carboxylate forms of 9-NC was studied. Then the lactone ratio vs time profiles of these 9-NC solutions were further investigated in pH 7.4 PBS, rat plasma and blood. 9-NC solutions with different lactone ratios (lactone ratios=100 %, 75 %, 50 %, 25 % and 0 %, respectively) were obtained by modifying the pH of solution and it was found that the effects on lactone/carboxylate equilibrium were in the order: blood cells > plasma albumin > pH. After i.v. administration, between the groups of 100 % and 75 % lactone ratios, the AUC0-t values of lactone 9-NC were almost equal. Therefore, there might be no difference between the anticancer activities of 9-NC solution in the range of 75~100 % lactone ratios. Colegio de Farmacéuticos de la Provincia de Buenos Aires