Relationship between lactone ratios of 9-nitrocamptothecin and their lactone/carboxylate equilibria in vitro and in vivo

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...

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Autores principales: Chen, Jun, Hu, Rongrong, Yang, Xixiong, Tian, Rong, Gu, Wei, Chen, Zhipeng, Cai, Baochang
Formato: Articulo
Lenguaje:Inglés
Publicado: 2012
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/25743
http://www.latamjpharm.org/resumenes/31/7/LAJOP_31_7_1_10.pdf
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Sumario: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.