Wang Su-Jun, Zeng Jie, Yang Ben-Kun, Zhong Yun-Ming
Department of Clinical Pharmacy, Guangdong Pharmaceutical University , Guangzhou , China.
Pharm Biol. 2014 Sep;52(9):1150-7. doi: 10.3109/13880209.2013.879906. Epub 2014 Mar 17.
Caffeic acid (CA) is widely distributed in edible plants, and it is beneficial to human health by exerting various biological effects. The potential pharmacological activities of CA are dependent on its absorption in the gastrointestinal tract.
To investigate the bioavailability of CA in rats and its absorption properties in the Caco-2 cell model.
A sensitive LC-MS/MS method was successfully applied to determine CA in rat plasma, perfusate, and Hank's balanced salt solution (HBSS). The absolute bioavailability (Fabs) of CA was obtained after i.v. (2 mg/kg) or i.g. administration (10 mg/kg) to rats. Blood samples (approximately 250 µL) were collected from the jugular vein catheter. Pharmacokinetic parameters were calculated using the 3P97 software (version 2.0 PK software; Chinese Society of Mathematical Pharmacology, Anhui, China). The intestinal absorption of CA was explored by the in situ vascularly perfused rat intestinal preparation. CA (5 mg/kg) was administered into the duodenum. Samples (250 µL) were collected from reservoir at specific times, and the same volume fresh perfusate was replaced. The Caco-2 cell model was applied to measure the permeability of CA from the apical to basolateral side (A → B) and from the basolateral to apical side (B → A).
The absolute bioavailability (Fabs) of CA was 14.7%, and its intestinal absorption was 12.4%. The Papp A→B values of CA were ranging from (4.87 ± 1.72) × 10(-7) cm/s to (5.05 ± 0.66) × 10(-7) cm/s as the concentration varied from 5 to 15 µg/mL.
CA was shown to have low oral bioavailability in rats, low intestinal absorption, and poor permeability across Caco-2 cells.
咖啡酸（CA）广泛分布于可食用植物中，通过发挥多种生物学效应而对人体健康有益。CA的潜在药理活性取决于其在胃肠道中的吸收情况。
研究CA在大鼠体内的生物利用度及其在Caco-2细胞模型中的吸收特性。
一种灵敏的液相色谱-串联质谱（LC-MS/MS）方法成功应用于测定大鼠血浆、灌流液和汉克平衡盐溶液（HBSS）中的CA。给大鼠静脉注射（2mg/kg）或灌胃给药（10mg/kg）后，获得CA的绝对生物利用度（Fabs）。从颈静脉导管采集血样（约250μL）。使用3P97软件（版本2.0 PK软件；中国数学药理学会，中国安徽）计算药代动力学参数。通过原位血管灌流大鼠肠道制剂研究CA的肠道吸收情况。将CA（5mg/kg）注入十二指肠。在特定时间从储液器采集样品（250μL），并替换相同体积的新鲜灌流液。应用Caco-2细胞模型测量CA从顶端到基底外侧（A→B）以及从基底外侧到顶端（B→A）的渗透率。
CA的绝对生物利用度（Fabs）为14.7%，其肠道吸收率为12.4%。当浓度从5μg/mL变化到15μg/mL时，CA的A→B方向的表观渗透系数（Papp）值范围为（4.87±1.72）×10⁻⁷cm/s至（5.05±0.66）×10⁻⁷cm/s。
结果表明，CA在大鼠体内口服生物利用度低，肠道吸收少，且透过Caco-2细胞的通透性差。
