Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats.
Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats.
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DOI：
10.1002/bdd.677
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发表时间：
2009-10
影响因子：
2.1
通讯作者：
Kong, Ah-Ng
中科院分区：
文献类型：
--
作者：
Barve, Avantika;Chen, Chi;Hebbar, Vidya;Desiderio, Joseph;Saw, Constance Lay-Lay;Kong, Ah-Ng
本研究的目的是比较山奈酚在大鼠肝脏和小肠的代谢，并研究山奈酚在大鼠体内的生物利用度和胃肠道的首过效应。用NADPH或UDPGA强化的肝脏和小肠微粒体与不同浓度的山奈酚孵育120分钟。根据动力学常数（Km和Vmax）的值，与nadph依赖的氧化代谢相比，肝脏和小肠微粒体中udpga依赖的偶联倾向更高。雄性Sprague-Dawley大鼠分别静脉注射山奈酚（10、25 mg/kg）或口服山奈酚（100、250 mg/kg）。口服山奈酚100 mg/kg后，通过采集门静脉血观察胃肠道首过效应。采用WinNonlin软件进行非区室分析获得药代动力学参数。静脉给药后，10和25 mg/kg的血药浓度-时间曲线具有高清除率（~ 3 L/hr/kg）和大体积分布（8 ~ 12 L/kg）的特点。该处置的特点是终端半衰期值为3-4小时。口服后血浆浓度-时间曲线显示吸收相当快（tmax ~ 1-2小时）。静脉给药和口服给药后，曲线下面积（AUC）值与剂量成正比增加。生物利用度(F)较差，约为2%。口服后门静脉血浆分析显示低至中度吸收。综上所述，山奈酚的低F部分归因于葡萄糖醛酸化和肠道和肝脏中其他代谢途径的广泛首过代谢。
The purpose of this study was to compare the hepatic and small intestinal metabolism, and examine bioavailability and gastro-intestinal first-pass effects of Kaempferol in the rats. Liver and small intestinal microsomes fortified with either NADPH or UDPGA were incubated with varying concentrations of Kaempferol for upto 120 minutes. Based on the values of the kinetic constants (Km and Vmax), the propensity for UDPGA-dependent conjugation as compared to NADPH-dependent oxidative metabolism was higher for both hepatic and small intestinal microsomes. Male Sprague-Dawley rats were administered Kaempferol intravenously (IV) (10, 25 mg/kg) or orally (100, 250 mg/kg). Gastro-intestinal first pass effects were observed by collecting portal blood after oral administration of 100 mg/kg Kaempferol. Pharmacokinetic parameters were obtained by Noncompartmental analysis using WinNonlin. After IV administration, the plasma concentration-time profiles for 10 and 25 mg/kg were consistent with high clearance (~ 3 L/hr/kg) and large volumes of distribution (8-12 L/kg). The disposition was characterized by a terminal half-life value of 3-4 hours. After oral administration the plasma concentration-time profiles demonstrated fairly rapid absorption (tmax ~ 1-2 hours). The area under the curve (AUC) values after IV and oral doses increased proportional to the dose. The bioavailability (F) was poor at ~ 2%. Analysis of portal plasma after oral administration revealed low to moderate absorption. Taken together, the low F of Kaempferol is attributed in part to extensive first-pass metabolism by glucuronidation and other metabolic pathways in the gut and in the liver.
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影响因子：
3.9
作者：
Shelby, MK;Cherrington, NJ;Klaassen, CD
通讯作者：
Klaassen, CD
影响因子：
6.1
作者：
Steensma, Aukje;Faassen-Peters, Maria A. W.;Rietjens, Ivonne M. C. M.
通讯作者：
Rietjens, Ivonne M. C. M.
影响因子：
7.1
作者：
Williamson, G;Manach, C
通讯作者：
Manach, C
影响因子：
4.2
作者：
Scalbert, A;Williamson, G
通讯作者：
Williamson, G
影响因子：
4.7
作者：
DuPont, MS;Day, AJ;Kroon, PA
通讯作者：
Kroon, PA