title: Quantitative Evaluation of the Mechanism Underlying the Biotransportation of the Active Ingredients in Puerariae lobatae Radix and Chuanxiong rhizoma.
abstract: The objective of this study was to establish a quantitative method to evaluate the biotransportation of a drug across the cell membrane. Through the application of the law of mass conservation, the drug transportation rate was calculated based on Fick's law of passive diffusion and the Michaelis-Menten equation. The overall membrane-transportation rate was the sum of the passive diffusion rate and the carrier-mediated diffusion rate, which were calculated as the transportation mass divided by the respective rate. The active ingredients of Puerariae lobatae Radix and Chuanxiong rhizoma, namely, puerarin and ferulic acid, respectively, were used as two model drugs. The transportation rates of puerarin and ferulic acid were obtained by fitting a model that includes both Fick's law of diffusion and the Michaelis-Menten equation. Compared with the overall transportation, the carrier-mediated transport and passive diffusion of 1.59 mmol/L puerarin were -35.07% and 64.93%, respectively, whereas the respective transportation modes of 0.1 mmol/L ferulic acid were -35.40% and 64.60%, respectively. Verapamil and MK-571 increased the overall transport rate and ratio, and MK-571 treatment changed the carrier-mediated transport from negative to positive. However, the transport rate and ratio of ferulic acid did not change significantly. The cell transportation mechanisms of puerarin and ferulic acid primarily involve simple passive diffusion and carrier-mediated transportation. Moreover, P-glycoprotein and multidrug resistance-associated protein efflux proteins, and other transportation proteins were found to be involved in the transportation of puerarin. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Key laboratory of Modern Preparation of TCM of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330003, Jiangxi, China.
authors.forename: Xin-Li
authors.initials: XL
authors.lastname: Liang
authors.affiliation: Key laboratory of Modern Preparation of TCM of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330003, Jiangxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key laboratory of Modern Preparation of TCM of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330003, Jiangxi, China.
authors.forename: Zheng-Gen
authors.initials: ZG
authors.lastname: Liao
authors.affiliation: Key laboratory of Modern Preparation of TCM of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330003, Jiangxi, China.
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Zhao
authors.affiliation: Key laboratory of Modern Preparation of TCM of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330003, Jiangxi, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Key laboratory of Modern Preparation of TCM of Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330003, Jiangxi, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, 27599, Chapel Hill, NC, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Satterlee
keywords: carrier-mediated diffusion; ferulic acid; passive diffusion; puerarin; quantitative evaluation