药物动力学的红霉素兔眼角膜后单剂注入:22的作用作为一个障碍体内眼部药物吸收。
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戴伊年代,Gunda年代,Mitra正义与发展党
药物动力学的红霉素兔眼角膜后单剂注入:22的作用作为一个障碍体内眼部药物吸收。
J Exp其他杂志》2004年10月,311 (1):246 - 55。Epub 2004 6月2。
- PubMed ID
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15175422 (在PubMed]
- 文摘
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射流泵等22 (P-gp)是药物输送的主要障碍。功能性22最近发现在角膜和角膜细胞系。因此,它是可能的,22可能限制体内眼部药物吸收,导致眼部生物利用度较低。实验设计使用新西兰白化(新西兰白人)兔子评估抑制剂P-gp流出增加药物的吸收。麻醉兔有恒定的局部注入((14)C)红霉素的存在和缺乏抑制剂。睾酮、异搏定、奎尼丁、环孢霉素被选为P-gp抑制剂。运输实验Madin-Darby犬肾细胞转染与人类凋亡基因(MDCK-MDR1)。红霉素MDCK-MDR1细胞表现出明显的流出,表明红霉素是一个很好的P-gp生长的基质。眼部使用局部单剂注入进行了药代动力学研究方法。观察最大抑制P-gp介导流出500 microM睾酮。 Area under the curve (AUC)(0- infinity ) of erythromycin with 500 microM testosterone was almost 4 times higher than AUC(0- infinity ) without any inhibitor. Rate of elimination (k(10)) for erythromycin and those with inhibitors was found to be similar (141 +/- 23 min), suggesting that elimination pathways were not altered. All the inhibitors were found to be nontoxic. Verapamil also inhibited the efflux pump with moderate change in AUC(0- infinity ) and C(max) compared with control. Thus, P-gp is found to be active in vivo, and it restricts topical erythromycin absorption across the cornea, which can be inhibited by known P-gp inhibitors. Therefore, ocular bioavailability of P-gp substrates can be significantly enhanced by proper selection of P-gp inhibitors.