title: Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats.
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 t1/2 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.
authors.affiliation: Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.|Department of Pharmaceutical Analysis, Second Military Medical University School of Pharmacy, Shanghai, 200433, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, 15260, USA.
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Pharmaceutical Analysis, Second Military Medical University School of Pharmacy, Shanghai, 200433, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical Analysis, Second Military Medical University School of Pharmacy, Shanghai, 200433, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics*; D031841:Aconitum / Q000737:chemistry; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods; D061585:Voltage-Gated Sodium Channel Agonists / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D000276:Adjuvants, Immunologic; D061585:Voltage-Gated Sodium Channel Agonists; C047307:benzoylaconine; C047306:aconine; D000157:Aconitine
keywords: LC-MS/MS; absorption; alkaloids; metabolic rate; pharmacokinetics