Disposition Kinetics of Cathinone and its Metabolites after Oral Administration in Rats.

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current drug metabolism Pub Date : 2024-01-01 DOI:10.2174/0113892002300638240513065512

Fahad Y Sabei, Ibrahim Khardali, Mohamed A Al-Kasim, Emad Sayed Shaheen, Magbool Oraiby, Ahmad Alamir, Banji David, Saeed Alshahrani, Abdulmajeed M Jali, Mohammed Attafi, Mohammed Y Albeishy, Ibraheem Attafi

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Abstract

Background: Cathinone is a natural stimulant found in the Catha edulis plant. Its derivatives make up the largest group of new psychoactive substances. In order to better understand its effects, it is imperative to investigate its distribution, pharmacokinetics, and metabolic profile. However, the existing literature on cathinone remains limited.

Objective: This study aimed to investigate the disposition kinetics and metabolic profile of cathinone and its metabolite cathine through a single oral dose of cathinone administration in rats.

Methods: Cathinone and cathine concentrations were identified and quantified using ion trap liquid chromatography- mass spectrometry (LC-IT/MS). The metabolic profile in the serum, brain, lung, liver, kidney, and heart was analyzed at specific time points (0, 0.5, 2.5, 6, 12, 24, 48, and 72 hours) using the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method.

Results: The highest concentration of cathinone was found in the kidney (1438.6 μg/L, which gradually decreased to 1.97 within 48 h and disappeared after 72 h. Cathinone levels in the lungs, liver, and heart were 859, 798.9, and 385.8 μg/L, respectively, within half an hour. However, within 2.5 hours, these levels decreased to 608.1, 429.3, and 309.1 μg/L and became undetectable after 24 h. In the rat brain, cathinone levels dropped quickly and were undetectable within six hours, decreasing from 712.7 μg/L after 30 min. In the brain and serum, cathine reached its highest levels at 2.5 hours, while in other organs, it peaked at 0.5 hours, indicating slower conversion of cathinone to cathine in the brain and serum.

Conclusion: This study revealed a dynamic interplay between cathinone disposition kinetics and its impact on organ-specific metabolic profiles in rats. These results have significant implications for drug development, pharmacovigilance, and clinical practices involving cathinone. Investigating the correlation between the changes in biomarkers found in the brain and the levels of cathinone and cathine is essential for informed decision- making in medical practices and further research into the pharmacological properties of cathinone.

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大鼠口服 Cathinone 及其代谢物的处置动力学

背景介绍Cathinone 是一种天然的兴奋剂，存在于 Catha edulis 植物中。其衍生物是新精神活性物质中最大的一类。为了更好地了解其作用，必须研究其分布、药代动力学和代谢概况。然而，现有关于卡西酮的文献仍然有限：本研究旨在通过大鼠单次口服卡西酮，研究卡西酮及其代谢物卡辛的分布动力学和代谢概况：采用离子阱液相色谱-质谱法（LC-IT/MS）对卡西酮和卡辛的浓度进行鉴定和定量。采用超高效液相色谱-四极杆飞行时间质谱法（UPLC-QTOF/MS）分析了特定时间点（0、0.5、2.5、6、12、24、48 和 72 小时）大鼠血清、脑、肺、肝、肾和心脏的代谢概况：肾脏中的卡西酮浓度最高（1438.6 μg/L），48 小时内逐渐降至 1.97，72 小时后消失。在大鼠大脑中，卡西酮水平迅速下降，30 分钟后从 712.7 微克/升下降到 6 小时内检测不到。在大脑和血清中，卡西酮在 2.5 小时后达到最高水平，而在其他器官中，卡西酮在 0.5 小时后达到峰值，这表明卡西酮在大脑和血清中转化为卡西酮的速度较慢：本研究揭示了卡西酮处置动力学与卡西酮对大鼠特定器官代谢特征的影响之间的动态相互作用。这些结果对涉及卡西酮的药物开发、药物警戒和临床实践具有重要意义。研究大脑中发现的生物标志物的变化与卡西酮和卡辛水平之间的相关性，对于在医疗实践中做出明智决策以及进一步研究卡西酮的药理特性至关重要。

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来源期刊

Current drug metabolism 医学-生化与分子生物学

CiteScore

4.30

自引率

4.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.