AMPIROXICAM, AN ANTIINFLAMMATORY AGENT WHICH IS A PRODRUG OF PIROXICAM
AMPIROXICAM, AN ANTIINFLAMMATORY AGENT WHICH IS A PRODRUG OF PIROXICAM
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DOI：
10.1007/bf01998969
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发表时间：
1993-07-01
期刊：
影响因子：
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通讯作者：
WEISSMAN, A
中科院分区：
文献类型：
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作者：
CARTY, TJ;MARFAT, A;WEISSMAN, A
安吡罗昔康是吡罗昔康的非酸性醚碳酸酯前药。我们的研究结果表明，与吡罗昔康相反，安吡罗昔康在体外不具有可检测的前列腺素合成抑制活性。然而，安吡罗昔康在抑制大鼠佐剂性关节炎的足肿胀方面具有与吡罗昔康相似的体内效力。在大鼠急性足炎症模型中，安吡罗昔康的效力低于吡罗昔康本身。在每日单次或多次（5次）口服给药后，安吡罗昔康的ED 50分别比吡罗昔康高9倍和3.5倍。采用苯基苯醌拉伸试验作为评价急性凝血活性的方法，安吡罗昔康的ED 50约为吡罗昔康的3倍。这些活性测试都具有部分依赖于胰高血糖素的特性。人经口给药后，在血浆中未观察到安吡昔康本身[24]，在本文报告的大鼠、犬和猴中也未观察到安吡昔康。生物利用度研究表明，在这四个物种中，吡罗昔康的转化率分别约为100%、90%、70%和50%。这些结果表明，安吡罗昔康的抗炎活性在体内通过转化为吡罗昔康而产生，并支持其作为吡罗昔康的有效前药的资格。
Ampiroxicam is a nonacidic ether carbonate prodrug of piroxicam. Our results demonstrate that, in contrast to piroxicam, ampiroxicam does not possess detectable prostaglandin synthesis inhibitory activity in vitro. Ampiroxicam, however, has similar in vivo potency to piroxicam in suppressing paw swelling in rat adjuvant arthritis. In an acute model of paw inflammation in rats, ampiroxicam is less potent than piroxicam itself. the ED50's of ampiroxicam are 9- and 3.5-fold higher than those of piroxicam following a single or multiple (5) daily oral doses, respectively. Using the phenylbenzoquinone stretching test as a method of evaluating acute analgetic activity, the ED50 for ampiroxicam is about 3-fold higher than that of piroxicam. These tests of activity share the property of being partially prostaglandin-dependent. Ampiroxicam itself is not observed in plasma after oral dosing to man [24], nor in the rat, dog, and monkey as reported here. Bioavailability studies show that conversion to piroxicam is about 100%, 90%, 70%, and 50% in these four species, respectively. These results indicate that ampiroxicam's anti-inflammatory activity is produced in vivo by conversion to piroxicam and support its credentials as an efficacious prodrug of piroxicam.