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首页> 外文期刊>Journal of pharmaceutical sciences. >Pharmacokinetics of oltipraz in mutant Nagase analbuminemic rats.
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Pharmacokinetics of oltipraz in mutant Nagase analbuminemic rats.

机译：奥立匹唑在突变的Nagase贫蛋白大鼠中的药代动力学。

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摘要

Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg) and oral (50 mg/kg) administration to control male Sprague-Dawely rats and mutant Nagase analbuminemic rats (NARs). In NARs, the expression and mRNA level of CYP1A2 increased, and oltipraz was mainly metabolized via CYP1A1/2, 2B1/2, 2C11, 201, and 3A1/2 in male rats. Hence, it may be expected that the CL of oltipraz would be significantly faster in NARs. This was proven by the following results. After intravenous administration, the CL of oltipraz was significantly faster in NARs (125% increase) than controls due to significantly greater free fractions (unbound to plasma proteins) of oltipraz (197% increase) and significantly faster CL(int) for the disappearance of oltipraz (11.4% increase) in NARs, since oltipraz is an intermediate hepatic extraction ratio drug in rats. The V(ss) was significantly larger in NARs (109% increase) and this could be due to significant increase in free fractions of oltipraz in NARs. After oral administration, the AUC of oltipraz was also significantly smaller in NARs (61.9% decrease). This could also be due to significant increase in free fractions of oltipraz and significantly faster CL(int) in NARs. However, this was not due to decrease in absorption in NARs.
机译：比较了静脉注射（10 mg / kg）和口服（50 mg / kg）来控制雄性Sprague-Dawely大鼠和突变的Nagase脱氨性大鼠（NARs）后oltipraz的药代动力学参数。在NARs中，雄性大鼠中CYP1A2的表达和mRNA水平升高，而奥替普拉主要通过CYP1A1 / 2、2B1 / 2、2C11、201和3A1 / 2代谢。因此，可以预期，在NAR中，oltipraz的CL会明显更快。以下结果证明了这一点。静脉给药后，由于奥替普拉斯的游离部分（未结合血浆蛋白）明显更大（增加197％），NAPs中奥替拉唑的CL明显比对照组快（增加了125％），并且消失的CL（int）明显更快。由于oltipraz是大鼠中肝提取比率中等的药物，因此NAR中的oltipraz（增加11.4％）。 NARs中的V（ss）显着较大（增加109％），这可能是由于NARs中奥替普拉的游离分数显着增加。口服后，在非酒精性脂肪性肝炎中，oltipraz的AUC也显着较小（降低了61.9％）。这也可能是由于oltipraz的游离级分显着增加以及NAR中的CL（int）明显更快。但是，这不是由于NAR中吸收的减少所致。

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