Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats. Issue 8 (11th September 2015)

• Record Type: Journal Article
• Authors: Zhang, Hai; Sun, Sen; Zhang, Wen; Xie, Xiangqun; Zhu, Zhenyu; Chai, Yifeng; Zhang, Guoqing
• Is Part Of: Drug testing and analysis. Volume 8:Issue 8(2016:Aug.)
• Page Start: 839
• Page End: 846
• Publication Date: 2015-09-11
• Subjects: absorption -- alkaloids -- LC‐MS/MS -- metabolic rate -- pharmacokinetics; Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.1858
• Languages: English
• ISSNs: 1942-7603

Abstract

Abstract : Aconitine (AC), benzoylaconine (BAC), and aconine (ACN) are three representative alkaloids in Aconitum tubers. Knowing that the drug disposal process in vivo is closely related to the toxicity and efficacy of a drug, it is important to classify the disposal properties of these alkaloids. In this study, the pharmacokinetics of the three alkaloids was investigated. The results showed that the three alkaloids could be quickly absorbed, especially BAC, whose Tmax was 0.31 ± 0.17 h. Their Cmax was 10.99, 3.99, and 4.29 ng·mL ‐1 respectively, indicating that AC had better absorption than BAC and ACN. Subsequently, we further investigated their absorption mechanism using the Caco‐2 cell monolayer model in vitro . The results showed that they were poorly absorbed, and the absorption of AC and BAC was inhibited by P‐gp, while the absorption of ACN was in a form of passive diffusion. The t 1 / 2 of AC, BAC and ACN was 1.41, 9.49, and 3.32 h, respectively, indicating that the metabolic or excretion rate of AC was quicker than that of BAC and ACN. Therefore, their metabolic stability was further investigated by using rat liver microsomes in vitro, which showed that AC was easier to be metabolized than BAC and ACN. The excretion experiments showed that AC and ACN were primarily excreted in urine, while BAC was excreted in faeces. In addition, the results of tissue distribution experiments showed that the three alkaloids distributed throughout all the organs, although the distribution rate of AC was slower than that of BAC and ACN. Copyright © 2015 John Wiley & Sons, Ltd. Abstract : A LC–MS/MS method to determine the 3 kinds of alkaloids in rat plasma, urine, feces, and different tissues after oral administration to rats had been developed, and then it was used to investigate the disposal process of 3 kinds of alkaloids in vivo . Comparing with the pharmacokinetic parameters, the absorption and metabolism mechanisms of 3 kinds of alkaloids were further clarified by using the Caco‐2 cell monolayer model and rat liver microsome incubation system in vitro .