Two Cases of Fatal Zopiclone Overdose

Boniface, Peter J.; Russell, Sarah

doi:10.1093/jat/20.2.131

Cited by 32 publications

(11 citation statements)

References 9 publications

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“…With increasing frequency of Z-drug prescriptions and abuse in Europe and North America, benzodiazepine screening tests that employ highly sensitive mass spectrometers are recommended to routinely include Z-drugs. Techniques used in the analysis and detection of Z-drugs in various biological matrices are shown in Table 3 [46][47][48][49][50][51][52].…”

Section: Analysis and Detection Of Z-drugsmentioning

confidence: 99%

“…In drug-facilitated crimes, where higher doses may have been administered, maximum recommended time intervals for Zdrug detection is 48 h in blood and 72 h in urine [54]. Therapeutic maximal concentrations (C max ) and those found in fatalities are shown in Table 4 [47,51,53,[55][56][57][58][59][60][61][62].…”

Section: Analysis and Detection Of Z-drugsmentioning

confidence: 99%

“…Comparative toxicity between the Z-drugs has been difficult to quantify due to the fact that the denominator is unknown. However, for zaleplon, the improved References include [46][47][48][49][50][51][52] ESI electrospray ionization, GC gas chromatography, HPLC high-performance liquid chromatography, LC liquid chromatography, LIF laserinduced fluorescence, LLE liquid-liquid extraction, MS mass spectroscopy, SPE solid-phase extraction, UV ultraviolet, PM postmortem, PMR postmortem redistribution Therapeutic maximal concentrations are in plasma and shown with corresponding administered doses (in parentheses). Postmortem levels are in whole blood; blood/plasma ratio for zopiclone and zaleplon is 1.…”

Section: Clinical Toxicology Of Z-drugsmentioning

confidence: 99%

“…Postmortem levels are in whole blood; blood/plasma ratio for zopiclone and zaleplon is 1. References include [47,51,53,[55][56][57][58][59][60][61][62] C max maximal concentration pharmacokinetic profile may contribute to its apparent lower rate of toxicity and fatalities; a confounder to this postulate is that the detection window is more limited and zaleplon ingestion may be missed. In an American Poison Control Center study, zolpidem overdose was more likely to lead to intensive care admission when co-ingested with over-thecounter cold and flu preparations, other psychotropic medication, or ethanol [69].…”

Section: Clinical Toxicology Of Z-drugsmentioning

confidence: 99%

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The Clinical and Forensic Toxicology of Z-drugs

Gunja

2013

J. Med. Toxicol.

161

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The Z-drugs zolpidem, zopiclone, and zaleplon were hailed as the innovative hypnotics of the new millennium, an improvement to traditional benzodiazepines in the management of insomnia. Increasing reports of adverse events including bizarre behavior and falls in the elderly have prompted calls for caution and regulation. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. Z-drugs exert their effects through increased γ-aminobutyric acid (GABA) transmission at the same GABA-type A receptor as benzodiazepines. Their pharmacokinetics approach those of the ideal hypnotic with rapid onset within 30 min and short half-life (1-7 h). Zopiclone with the longest duration of action has the greatest residual effect, similar to short-acting benzodiazepines. Neuropsychiatric adverse events have been reported with zolpidem including hallucinations, amnesia, and parasomnia. Poisoning with Z-drugs involves predominantly sedation and coma with supportive management being adequate in the majority. Flumazenil has been reported to reverse sedation from all three Z-drugs. Deaths from Z-drugs are rare and more likely to occur with polydrug overdose. Zdrugs can be detected in blood, urine, oral fluid, and postmortem specimens, predominantly with liquid chromatography-mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Zaleplon with its ultra-short half-life has been detected in few clinical or forensic cases possibly due to assay unavailability, low frequency of use, and short window of detection. Though Z-drugs have improved pharmacokinetic profiles, their adverse effects, neuropsychiatric sequelae, and incidence of poisoning and death may prove to be similar to older hypnotics.

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Section: Analysis and Detection Of Z-drugsmentioning

confidence: 99%

Section: Analysis and Detection Of Z-drugsmentioning

confidence: 99%

Section: Clinical Toxicology Of Z-drugsmentioning

confidence: 99%

Section: Clinical Toxicology Of Z-drugsmentioning

confidence: 99%

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The Clinical and Forensic Toxicology of Z-drugs

Gunja

2013

J. Med. Toxicol.

161

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“…The number of ZOP cases and the concentrations in blood in cases of drug-related violent crimes in Sweden 2008 to 2013 are shown in Table 3. Fatalities resulting from poisoning with ZOP combined with alcohol or other drugs have also been described [73,[112][113][114][115] and cases of fatal ZOP overdose with ZOP concentrations of 1.4-3.9 mg/L in the blood have been reported [116]. An overdose death after ingesting 90 mg of ZOP suggested that this amount could be a minimum lethal dose (in femoral blood the ZOP concentration was 0.254 mg/L) [114].…”

Section: Occurrence Of Zopiclone In Forensic Casesmentioning

confidence: 99%

Zopiclone degradation in biological samples : Characteristics and consequences in forensic toxicology

Nilsson¹

2014

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Drug concentrations in post‐mortem specimens

Ketola

Kriikku

2019

Drug Testing and Analysis

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A meta‐analysis of drug concentrations in post‐mortem specimens is presented. The analysis involved 50 commonly used drugs and their concentrations in femoral blood, other blood (such as cardiac blood), vitreous humor, muscle, liver, kidney, brain, heart, lung, spleen, and bile. A total of 10 993 analytical results from 5375 post‐mortem cases in 388 studies were gathered and the ratios of drug concentrations in tissue material to median femoral blood concentrations were calculated. Analytical results from the laboratory's own database (years 2000–2018) were also included. The results show that the variation of ratios between post‐mortem specimens and femoral blood is highly compound dependent. This database can be utilized in interpretation of toxicological results in cases where femoral blood is not available. The specimens with similar concentrations as in femoral blood were vitreous humor, muscle, and other blood, such as cardiac blood, and the highest concentrations were generally measured from liver and bile. For these reasons we suggest the following order for biological specimens to be used for a quantitative toxicological analysis in cases where femoral blood is not available: 1. other blood, 2. muscle, 3. vitreous humor, 4. brain, 5. heart, 6. spleen, 7. kidney, 8. liver, and 9. bile.

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Two Cases of Fatal Zopiclone Overdose

Cited by 32 publications

References 9 publications

The Clinical and Forensic Toxicology of Z-drugs

The Clinical and Forensic Toxicology of Z-drugs

Zopiclone degradation in biological samples : Characteristics and consequences in forensic toxicology

Drug concentrations in post‐mortem specimens

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