Effects of long-term administrations of aconitine on electrocardiogram and tissue concentrations of aconitine and its metabolites in mice

Wada, Kentaro; Nihira, Makoto; Hayakawa, Hideyuki; Tomita, Y; Hayashida, Makiko; Ohno, Youkichi

doi:10.1016/j.forsciint.2004.04.016

Cited by 82 publications

(48 citation statements)

References 10 publications

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“…Some researchers have reported that Aconitum alkaloids were absorbed very quickly while the bioavailability was very low. [12,[18][19][20] Although many pharmacological studies on Aconitum alkaloids have been reported, [21][22][23][24][25] there are few systematic studies available on the pharmacokinetic characteristics and disposal process of the three forms of Aconitum alkaloids. The aim of this study was to determine the biological activities of three forms of Aconitum alkaloids in rat plasma, urine, faeces, and different tissues after oral administration by liquid chromatographytandem mass spectrometry (LC-MS/MS), investigate their disposal process in vivo, and clarify their pharmacokinetic parameters, absorption and metabolic stability by using a Caco-2 cell monolayer model and rat liver microsome incubation system in vitro, hoping that this study would provide references for rational clinical use of the Aconitum tuber, and for further research on the pharmacology or toxicology of this medicinal plant.…”

Section: Introductionmentioning

confidence: 99%

Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

Hai

Sun

Zhang

et al. 2015

Drug Testing and Analysis

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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.

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Section: Introductionmentioning

confidence: 99%

Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

Hai

Sun

Zhang

et al. 2015

Drug Testing and Analysis

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“…After metabolism, aconitine is detoxicated. Wada et al (2005) reported that oral LD 50 of benzoylaconine in Institute of Cancer Research (ICR) mice was 1500 mg/kg, and that of aconine was 17.42 g/kg.…”

Section: Introductionmentioning

confidence: 99%

Study of Aconitine toxicity in rat embryos in vitro

Xiao¹,

Wang²,

Liu³

et al. 2007

Birth Defects Research Pt B

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“…Aconitine poisoning is most frequently caused by accidental ingestion, as it can be mistaken for an edible grass and by the use of herbal medicines, mainly in Asian countries where these are more used [7, 8, 23-25, 35, 40, 41]. A few fatal accidents have been reported [5,7,8,14,17,35,36,41], and as it is highly toxic, aconitine or Aconitum species are sometimes used in suicides and homicides [11-13, 20, 28, 36]. Even in ancient times it was known as a poison [29].…”

Section: Introductionmentioning

confidence: 99%

Aconitine involvement in an unusual homicide case

et al. 2006

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We describe a homicide complicated by an aconitine poisoning, which was initially thought to be a strangulation case. Routine toxicological analyses demonstrated only a small amount of alcohol in the blood and the urine. The case could not be clarified until 5 years after the event. A new element in the investigation made the wife the prime suspect, and finally, after thorough interrogation, she confessed her crime. She had mixed a decoction of three plants of Aconitum with red wine. Additional toxicological analyses, using the liquid chromatography-tandem mass spectrometry (LC-MS-MS) technique demonstrated 810 ng/ml of aconitine in urine, 6.5 ng/g in liver and 1.3 ng/g in the kidneys. Even though aconitine poisoning is still rare in Europe, it should be taken into account in suicides and homicides, particularly in unclarified cases.

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Effects of long-term administrations of aconitine on electrocardiogram and tissue concentrations of aconitine and its metabolites in mice

Cited by 82 publications

References 10 publications

Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats

Study of Aconitine toxicity in rat embryos in vitro

Aconitine involvement in an unusual homicide case

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