Beránková Katerina, Szkutová Miroslava, Balíková Marie
Institute of Forensic Medicine and Toxicology, 1st Medical Faculty, Charles University in Prague, Prague, Czech Republic.
Forensic Sci Int. 2007 Aug 6;170(2-3):94-9. doi: 10.1016/j.forsciint.2007.03.023. Epub 2007 Jul 12.
2,5-Dimethoxy-4-bromoamphetamine (DOB) is one of the potent hallucinogenic phenylalkylamines, whose ingestion has already caused several deaths reported all over the world. However, there is insufficient information on DOB properties based on controlled pharmacokinetic studies available. The aim of this study was to clarify the distribution profile of DOB and its phenolic metabolite 2-methoxy-5-hydroxy-4-bromoamphetamine (2M5H4BA) in blood and biological tissues of experimental rats. The rats were administered a 20 mg/kg dose of DOB.HCl by oral ingestion or subcutaneous injection. Plasma and brain, liver and lung tissues were collected at 0.5, 1, 2, 4, 8, 16, and 32 h after dosing (three animals per time point). The samples were prepared by a liquid-liquid extraction procedure and the extracts were assayed by GC-MS. After per oral application, DOB peak plasma level of 320 ng/mL was reached after one-hour post dosing as well as 2M5H4BA peak concentration of 203 ng/mL. A rapid phase of DOB absorption, 2M5H4BA formation and their tissue distribution during the first two hours after application were followed by a slow decrease rate of the elimination process until 32 h. After subcutaneous application, high plasma levels of the unchanged parent drug and relatively reduced formation of its metabolite 2M5H4BA were observed. DOB maximum plasma concentration of 1143 ng/mL was reached after one-hour post application, whereas its metabolite peak level after 8 h was 213 ng/mL. The concentration profiles of both compounds in plasma after per oral and subcutaneous administration revealed the existence of significant first pass effect after per oral administration that significantly affected DOB bioavailability. DOB tissue concentrations exceeded plasma and the highest values were found in the lungs, where drug accumulation occurred with prolonged retention till 32 h after subcutaneous dose. Although the plasma/tissue transfer was more effective for the lipophilic parent drug than for its hydroxylated metabolite 2M5H4BA, the metabolite tissue levels were significant. The hallucinogenic potential of 2M5H4BA appearing in brain remains unclear as nothing is known about its pharmacological activity at present.
2,5-二甲氧基-4-溴苯丙胺（DOB）是一种强效致幻性苯烷基胺，其摄入已在全球范围内导致多起死亡报告。然而，基于可控药代动力学研究的关于DOB特性的信息并不充分。本研究的目的是阐明DOB及其酚类代谢物2-甲氧基-5-羟基-4-溴苯丙胺（2M5H4BA）在实验大鼠血液和生物组织中的分布情况。通过口服或皮下注射给大鼠施用20mg/kg剂量的DOB·HCl。在给药后0.5、1、2、4、8、16和32小时收集血浆以及脑、肝和肺组织（每个时间点三只动物）。样品通过液液萃取程序制备，提取物通过气相色谱-质谱联用仪进行分析。口服给药后，给药后1小时达到320ng/mL的DOB血浆峰值水平以及203ng/mL的2M5H4BA峰值浓度。在给药后的前两小时内，DOB吸收、2M5H4BA形成及其组织分布的快速阶段之后是消除过程的缓慢下降速率，直至32小时。皮下给药后，观察到未变化的母体药物的高血浆水平以及其代谢物2M5H4BA的相对减少的形成。给药后1小时达到1143ng/mL的DOB最大血浆浓度，而其代谢物在8小时后的峰值水平为213ng/mL。口服和皮下给药后血浆中两种化合物的浓度曲线表明口服给药后存在显著的首过效应，这显著影响了DOB的生物利用度。DOB组织浓度超过血浆浓度，在肺中发现最高值，皮下给药后药物在肺中蓄积并长时间保留直至32小时。尽管亲脂性母体药物的血浆/组织转运比其羟基化代谢物2M5H4BA更有效，但代谢物的组织水平也很显著。出现在脑中的2M5H4BA的致幻潜力仍不清楚，因为目前对其药理活性一无所知。
