Biliary Excretion of Diazepam and its Metabolites in Man

Sellman, R.; Kanto, J.; Pekkarinen, J.

doi:10.1111/j.1600-0773.1975.tb00841.x

Cited by 15 publications

(3 citation statements)

References 19 publications

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“…This suggests the uptake of flubromazepam within a short period of time before the first blood sampling. The concentration course supports the assumption of an enterohepatic circulation as previously suggested for flubromazepam and shown before for diazepam . Though flubromazepam has been marketed as a new psychoactive substance (NPS) for about 4 years (first EMCDDA report in 2013), there were only few reports on poisonings.…”

Section: Discussionsupporting

confidence: 85%

Mixed intoxication by the synthetic opioid U‐47700 and the benzodiazepine flubromazepam with lethal outcome: Pharmacokinetic data

Koch

Auwärter

Hermanns-Clausen

et al. 2018

Drug Testing and Analysis

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Novel synthetic opioids and benzodiazepines are an emerging trend on the narcotic drugs market. We present a lethal case of U-47700 and flubromazepam poisoning. A 24-year-old man suffered apnoea after the consumption of the synthetic opioid U-47700 in combination with the benzodiazepine flubromazepam. After reanimation and hospital admission, hypoxic cerebral damage and severe brain oedema were stated. Six days after admission, mechanical ventilation was discontinued, and the patient died. Seven blood serum samples and one urine sample collected during the hospitalisation were analysed by liquid chromatography-tandem mass spectrometry. In the sample collected 42 minutes after admission, the concentrations of U-47700 and flubromazepam were 370 and 830 ng/mL, respectively. Three days later, the concentrations of U-47700 and flubromazepam dropped to 4.2 and 280 ng/mL, respectively. The resulting concentration-time-curves allowed calculating a U-47700 elimination half-life of approximately six hours and confirmed the previously reported flubromazepam elimination half-life of around 100 hours. In the presented case, intoxication by the synthetic opioid U-47700 with a contribution of flubromazepam can be assumed as the cause of death. The concentration-time curves allow an estimation of the clinical course of similar cases. Flubromazepam may lead to prolonged central-nervous depressant effects.

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Section: Discussionsupporting

confidence: 85%

Mixed intoxication by the synthetic opioid U‐47700 and the benzodiazepine flubromazepam with lethal outcome: Pharmacokinetic data

Koch

Auwärter

Hermanns-Clausen

et al. 2018

Drug Testing and Analysis

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“…A possible explanation for this plateau phase could be an enterohepatic circulation as it has been suggested and shown for e.g. diazepam . This relatively long elimination half‐life along with the prolonged duration of effects particularly bear health risks in cases of consumers driving a vehicle or operating heavy machinery in the days following consumption.…”

Section: Resultsmentioning

confidence: 99%

“…diazepam. [16,17] This relatively long elimination half-life along with the prolonged duration of effects particularly bear health risks in cases of consumers driving a vehicle or operating heavy machinery in the days following consumption.…”

Section: Analysis Of the Serum Samplesmentioning

confidence: 99%

Detection and identification of the designer benzodiazepine flubromazepam and preliminary data on its metabolism and pharmacokinetics

et al. 2013

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The appearance of pyrazolam in Internet shops selling 'research chemicals' in 2012 marked the beginning of designer benzodiazepines being sold as recreational drugs or 'self medication'. With recent changes in national narcotics laws in many countries, where two uncontrolled benzodiazepines (phenazepam and etizolam), which were marketed by pharmaceutical companies in some countries, were scheduled, clandestine laboratories seem to turn to poorly characterized research drug candidates as legal substitutes. Following the appearance of pyrazolam, it comes with no surprise that recently, flubromazepam (7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one), a second designer benzodiazepine, was offered on the market. In this article, this new compound was characterized using nuclear magnetic resonance, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS/MS) and liquid chromatography quadrupole time-of-flight MS (LC-Q-ToF-MS). Additionally, a study was carried out, in which one of the authors consumed 4 mg of flubromazepam to gain preliminary data on the pharmacokinetic properties and the metabolism of this compound. For this purpose, serum as well as urine samples were collected for up to 31 days post-ingestion and analyzed applying LC-MS/MS and LC-Q-ToF-MS techniques. On the basis of this study, flubromazepam appears to have an extremely long elimination half-life of more than 100 h. One monohydroxylated compound and the debrominated compound could be identified as the predominant metabolites, the first allowing a detection of a consumption for up to 28 days post-ingestion when analyzing urine samples in our case. Additionally, various immunochemical assays were evaluated, showing that the cross-reactivity of the used assay seems not to be sufficient for safe detection of the applied dose in urine samples, bearing the risk that it could be misused in drug-withdrawal settings or in other circumstances requiring regular drug testing. Furthermore, it may be used in drug-facilitated crimes without being detected.

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