KINETICS AND MECHANISM OF UPTAKE OF PLATINUM-BASED PHARMACEUTICALS BY THE RAT SMALL-INTESTINE
KINETICS AND MECHANISM OF UPTAKE OF PLATINUM-BASED PHARMACEUTICALS BY THE RAT SMALL-INTESTINE
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DOI：
10.1016/0006-2952(90)90400-f
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发表时间：
1990-09-15
影响因子：
5.8
通讯作者：
DOBROTA, M
中科院分区：
文献类型：
--
作者：
BINKS, SP;DOBROTA, M
使用体外和原位模型研究了两种铂类药物顺铂和卡铂的吸收。通过利用外翻的大鼠小肠，人们发现，这两种药物的吸收与时间呈线性长达60分钟，是不饱和的浓度为1.0 mM。此外，不能证明对浓度梯度的吸收和吸收不会减少代谢抑制或缺氧条件。这些结果表明顺铂和卡铂缺乏主动转运机制，并暗示通过胃肠道的吸收是被动扩散。顺铂比卡铂更容易吸收，无论是在体外还是在原位。在原位发现两种药物从肠腔消失后，一级动力学。原位研究的结果表明，灌注介质的pH值降低导致卡铂吸收到全身血液中的增加。本报告确立了顺铂和卡铂均通过胃肠道吸收的事实，并表明涉及口服铂类药物的临床前试验是合理的。
The absorption of two platinum-based pharmaceuticals, cisplatin and carboplatin, was studied using in vitro and in situ models. By utilizing everted rat small intestine, it was found that absorption of both drugs was linear with time up to 60 min and was not saturable up to a concentration of 1.0 mM. Moreover, uptake against a concentration gradient could not be demonstrated and absorption was not reduced by metabolic inhibition or anoxic conditions. These results indicate the lack of involvement of an active transport mechanism for cisplatin and carboplatin and imply that absorption across the gastrointestinal tract is by passive diffusion. Cisplatin was absorbed more readily than carboplatin, both in vitro and in situ. In situ both drugs were found to disappear from the intestinal lumen following first-order kinetics. The results of in situ studies indicate that a decrease in pH of the perfusion medium leads to an increase in absorption of carboplatin into the systemic blood. This report establishes the fact that both cisplatin and carboplatin are absorbed across the gastro-intestinal tract and indicates that preclinical trials involving oral administration of platinum-based pharmaceuticals could be justified.