Li Hewei, Dong Ling, Liu Yang, Wang Gang, Zhang Lei, Qiao Yanjiang
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, PR China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, PR China.
J Pharmacol Toxicol Methods. 2014 Jul-Aug;70(1):6-11. doi: 10.1016/j.vascn.2014.03.170. Epub 2014 Mar 25.
Everted gut sac (EGS) and in situ single-pass intestinal perfusion (SPIP) have been widely used in the study of drug absorption and biopharmaceutical classification systems (BCS). Furthermore, they could also be applied in the research of drug intestinal first-pass metabolism. Since most of Chinese herbal medicines (CHMs) are orally administrated, it is necessary to study the permeability of active ingredients of CHMs. Thus, we attempted to apply the EGS and SPIP models to study the permeability of puerarin, one of the active marker compounds (AMCs) of Puerariae Radix.
In the present study, three rat models of ex vivo and in situ, EGS, SPIP, and in situ intestinal perfusion with venous sampling (IPVS), were established to determine the permeability coefficient of puerarin. The apparent permeability coefficient (Papp) was obtained by EGS. The SPIP model was used to determine the effective permeability coefficient (Peff) in different intestinal segments. The blood permeability coefficient (Pblood) was determined by IPVS. Puerarin concentration of perfusion and blood samples were measured by HPLC.
Puerarin could filter into EGS incubated in aqueous extract of Puerariae Radix or puerarin solution. In the SPIP experiment, the concentration effect on Peff was observed in the ileum, but not in the other three intestinal segments. The Pblood was 0.068±0.002×10(-5)cm/s and was 16-fold lower than the Peff (1.114±0.153×10(-5)cm/s) in the IPVS experiment at 80μg/mL puerarin. As expected, the Peff (1.24±0.11×10(-5)cm/s) in SPIP did not differ from the Peff in IPVS. The Papp was 0.199×10(-5)cm/s at 1200μg/mL puerarin, 10-fold lower than Peff (2.047±0.116×10(-5)cm/s) in SPIP.
Three models for permeability were successfully practiced in the study of puerarin absorption and our research strategy will be useful for herbal constituent absorption in the future.
外翻肠囊（EGS）和原位单通道肠道灌注（SPIP）已广泛应用于药物吸收和生物药剂学分类系统（BCS）的研究。此外，它们也可应用于药物肠道首过代谢的研究。由于大多数中药是口服给药，因此有必要研究中药活性成分的渗透性。因此，我们尝试应用EGS和SPIP模型研究葛根活性标记化合物之一葛根素的渗透性。
在本研究中，建立了三种大鼠离体和原位模型，即EGS、SPIP和原位肠道灌注静脉取样（IPVS），以测定葛根素的渗透系数。通过EGS获得表观渗透系数（Papp）。SPIP模型用于测定不同肠段的有效渗透系数（Peff）。通过IPVS测定血液渗透系数（Pblood）。灌注液和血样中的葛根素浓度通过高效液相色谱法测定。
葛根素可滤入在葛根水提取物或葛根素溶液中孵育的EGS。在SPIP实验中，在回肠观察到浓度对Peff的影响，但在其他三个肠段未观察到。在80μg/mL葛根素的IPVS实验中，Pblood为0.068±0.002×10(-5)cm/s，比Peff（1.114±0.153×10(-5)cm/s）低16倍。正如预期的那样，SPIP中的Peff（1.24±0.11×10(-5)cm/s）与IPVS中的Peff没有差异。在1200μg/mL葛根素时，Papp为0.199×10(-5)cm/s，比SPIP中的Peff（2.047±0.116×10(-5)cm/s）低10倍。
在葛根素吸收研究中成功实施了三种渗透性模型，我们的研究策略将对未来草药成分的吸收研究有用。
