Distribution of zolpidem in body fluids and organ tissues in five autopsy cases

Takayasu, Tatsunori; Ishida, Yuko; Kimura, Akihiko; Kawaguchi, Mariko; Kondo, Toshikazu

doi:10.1007/s11419-008-0055-9

Cited by 19 publications

(19 citation statements)

References 17 publications

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“…Levine et al did not find postmortem redistribution of zolpidem in three cases with cardiac/femoral blood concentration ratios ranging from 0.8 to 0.9 [14]. Takayasu et al found differences in blood and organ tissue concentration for zolpidem in postmortem cases but did not explicitly refer these results to postmortem redistribution [26]. Indeed, our results point to a postmortem redistribution of zolpidem after only a short postmortem interval.…”

Section: Discussioncontrasting

confidence: 81%

A suicide involving intraperitoneal injection of pentobarbital

et al. 2015

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We present an unusual case of suicide by intraperitoneal injection of pentobarbital, an overdose of zolpidem and the intake of diazepam, ethanol and other psychoactive substances. The autopsy and specimen collection were conducted in a 10 to 18 h postmortem interval. The toxicological analysis revealed a significantly higher pentobarbital concentration in femoral blood compared to cardiac blood (36 vs. 15 mg/L). On the contrary, zolpidem and diazepam concentrations in cardiac blood (2700 and 590 µg/L) were found to be significantly higher than in femoral blood (1500 and 230 µg/L). These findings point to a postmortem redistribution with a distinct gradient from areas of high drug concentrations in the gastrointestinal tract (zolpidem and diazepam) and the injection site (pentobarbital) to peripheral tissue. Ethanol concentration was 0.95 ‰ which amplified the CNS depression. The choice of this unusual suicide method was associated with the deceased's former job as a veterinarian's assistant. In veterinary medicine, the intraperitoneal injection of a lethal dose of pentobarbital is quite commonly performed to euthanise small animals. Intraperitoneal injection is rare as route of administration in humans.

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Section: Discussioncontrasting

confidence: 81%

A suicide involving intraperitoneal injection of pentobarbital

et al. 2015

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“…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%

“…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%

The Clinical and Forensic Toxicology of Z-drugs

Gunja

2013

J. Med. Toxicol.

164

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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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“…A model Trace GC-MS system (ThermoFisher Scientifi c, Waltham, MA, USA) was used for analysis in the positive electron-impact (EI) mode [11,12]. The ionization voltage and ionization current were set at 70 eV and 0.15 mA, respectively.…”

Section: Gc-ms Conditionsmentioning

confidence: 99%