• Sleep Medicine and Psychophysiology
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• v.18 no.1
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• pp.5-9
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• 2011

Sleep-related eating disorder (SRED) is a newly recognized parasomnia that describes a clinical condition of compulsive eating under an altered level of consciousness during sleep. Recently, it is increasingly recognized in clinical practice. The exact etiology of SRED is unclear, but it is assumed that SRED might share features of both sleepwalking and eating disorder. There have been also accumulating reports of SRED related to the administration of various psychotropic drugs, such as zolpidem, triazolam, olanzapine, and combinations of psychotropics. Especially, zolpidem in patients with underlying sleep disorders that cause frequent arousals, may cause or augment sleep related eating behavior. A thorough sleep history is essential to recognition and diagnosis of SRED. The timing, frequency, and description of food ingested during eating episodes should be elicited, and a history of concurrent psychiatric, medical, sleep disorders must also be sought and evaluated. Interestingly, dopaminergic agents as monotherapy were effective in some trials. Success with combinations of dopaminergic and opioid drugs, with the addition of sedatives, has also been reported in some case reports.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.343-348
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• 2006

The purpose of the present study was to evaluate the bioequivalence of two zolpidem tartrate tablets, Stilnox tablet(Sanofi-aventis Korea, reference product) and Zanilo tablet(ChoDang Pharm Co., Ltd., Korea, test product), according to the guidelines of Korea Food and Drug Administration(KFDA). After adding an internal standard(cimetropium), 250 ${\mu}L$ plasma samples were extracted using 1.3 mL of ethyl acetate. Extracted compounds were analyzed by HPLC with triple-quadrupole mass spectrometry. This method for determination of zolpidem is proved accurate and reproducible with the limit of quantitation of 1 ng/mL in human plasma. Twenty-four healthy male Korean volunteers received each medicine at the zolpidem tartrate dose of 10 mg in a $2{\times}2$ crossover study. There was one-week washout period between the doses. Plasma concentrations of zolpidem were monitored for over a period of 8 hr after the administration. $AUC_{0-t}$(the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$(maximum plasma drug concentration) and $T_{max}$(time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_{0-t}$ and $C_{max}$. No significant sequence effect was found for all of the bio-availability parameters indicating that the crossover design was properly performed. The 90% confidence intervals for the log transformed data were acceptable range of log 0.8 to log 1.25(e.g., log 0.92-log 1.06 for $AUC_{0-t}$, log 0.96-log 1.13 for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that Zanilo tablet is bioequivalent to Stilnox tablet.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.191-196
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• 2011

In this study simple and sensitive high performance liquid chromatographic method using a commercially available column, was developed and validated for the determination of zolpidem tartrate in human plasma. The developed method with suitable validation was applied to a bioequivalence study of two different kinds of zolpidem tartrate. Two different formulations containing 10 mg of zolpidem tartate (CAS : 99294-93-6) were compared in 24 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, cross-over design in 24 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 12 h. The mean $AUC_{0-12h}$, $C_{max}$, $T_{max}$ and $T_{1/2}$ were $676.6{\pm}223.4$ $ng{\cdot}h{\cdot}mL^{-1}$, $177.4{\pm}34.2$ $ng{\cdot}mL^{-1}$, and $0.8{\pm}0.4$ and $3.5{\pm}2.1$, respectively, for the test formulations, and $640.7{\pm}186.6$ $ng{\cdot}h{\cdot}mL^{-1}$, $193.0{\pm}64.5$ $ng{\cdot}mL^{-1}$, and $0.9{\pm}0.4$ and $2.7{\pm}0.9$, respectively, for the reference formulation. Both primary target parameters $AUC_{0-12h}$ and $C_{max}$ were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of $AUC_{0-12h}$ and $C_{max}$ were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of zolpidem tartate are considered to be bioequivalent.

• Journal of The Korean Society of Clinical Toxicology
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• v.20 no.1
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• pp.8-14
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• 2022

Purpose: This study was undertaken to investigate how sedative-hypnotics affect the occurrence and severity of the patient's symptoms. In addition, we conducted a study to determine the type of patients who reacted severely and required hospitalization; patients were accordingly classified as hospitalized patients and patients discharged from the emergency room. Methods: From January 2017 to December 2019, we investigated the demographics, drug information, history, laboratory tests, and severity of patients who visited our emergency department and were diagnosed with benzodiazepine, zolpidem, and doxylamine succinate overdose. We further compared details of hospitalized patients and discharged patients. Results: Subjects who had overdosed and visited the ED included 120 for benzodiazepine, 147 for zolpidem, and 27 for doxylamine succinate. Comparisons between the three groups revealed differences in their early diagnosis, psychiatric history, and sleep disturbance. Differences between groups were also determined for mental state, poisoning history, treatment received in the intensive care unit, and intubation and ventilator support. In cases of benzodiazepine overdose, we obtained a high hospitalization rate (40.0%), admission to the intensive care unit (24.2%), and intubation rate (18.3%). Comparisons between hospitalized patients and discharged groups showed differences in transferred patients, early diagnosis, and mental state. Conclusion: Patients poisoned by sedative-hypnotics are increasing every year. In cases of benzodiazepine and zolpidem, the hospitalization rates were high, and benzodiazepine overdose resulted in hospitalization, intensive care unit admission, and pneumonia in a majority of cases. Therefore, active treatment and quick decisions in the emergency room are greatly required.

• Journal of Electrochemical Science and Technology
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• v.7 no.1
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• pp.68-75
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• 2016

In this study a new, simple, precise, accurate and economic electrochemical method was developed and validated for the voltammetric determination of zolpidem (ZP) using disposable pencil graphite (PG) electrode. The anodic oxidation of ZP on the surface of the PG electrode was examined in a britton robinson (BR) buffer. Square wave and cyclic voltammetry were used as electrochemical techniques in the potential range of 0-1.2 V in the pH 8 BR buffer. In cyclic voltammetry studies, the diffusion coefficient of ZP oxidation was found to be 3.6×10^-6 cm² s^-1. On the other hand, the ZP has shown a well-defined irreversible anodic peak at 0.98 V in the square wave voltammetry mode. The PG electrode, primarily being graphite which has a large active surface area gives rise to increasing peak current with respect to ZP electrooxidation. PG electrode showed an electrocatalytic effect in anodic oxidation of ZP. A linear relationship between catalytic current response and ZP concentration was obtained over a concentration range of 10-30 μM with R.S.D. values ranging from 0.29-3.89. Limits of detection and quantitation were found to be 1 and 3 μM, respectively. Finally, the PG electrode was successfully used to determine ZP in standard and tablet dosage forms with a mean recovery of 100.69 %.

• Sleep Medicine and Psychophysiology
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• v.6 no.1
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• pp.5-18
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• 1999

A growing number of people are concerned about their sleep. There are many people with chronic sleep disorders. Sedativehypnotics including benzodiazepine and non-benzodiazepine have been widely used in chronic insomniacs. It is widely accepted that current hypnotics are efficient in alleviating subjective symptoms of insomnia. Non-benzodiazepine hypnotics include zolpidem, zopiclone, and melatonin. These novel non-benzodiazepine hypnotics that have efficacy comparable to benzodiazepines were developed with more understanding of benzodiazepine receptor pharmacology. Their unique pharmacologic profiles may offer few significant advantages in terms of adverse effects of benzodiazepines. However, most of hypnotics including non-benzodiazepine have some of dependence, tolerance, impaired daytime function and rebound insomnia. Currently, it is accepted that combination therapy with pharmacologic and behavioral intervention is the most effective for chronic insomniacs.

• Journal of The Korean Society of Clinical Toxicology
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• v.7 no.1
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• pp.44-46
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• 2009

Herein, we report a case of emergency cesarean section after severe maternal drug intoxication in late pregnancy. At a 38-week-gestation, a 32-year-old woman with a 10-year history of bipolar disorder took olanzapine (200 mg), diazepam (20 mg), and zolpidem (200 mg) as part of a suicidal attempt. Given her unconscious state and the evident concern regarding the toxic effects of the drugs on the fetus, a cesarean section was performed immediately. The patient gave birth to a male baby with Apgar scores of 5 at 1 and 8 at 5 minutes. The baby showed dyspnea and decreased activity directly after birth. After supportive care, the condition of both mother and baby improved and both were discharged.

• Journal of The Korean Society of Clinical Toxicology
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• v.15 no.2
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• pp.101-106
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• 2017

Purpose: This study examined the patterns of drugs, poisons, and chemicals detected in autopsy samples performed in the Seoul Institute and other regional forensic offices of the National Forensic Service (NFS) between 2014 and 2016. Methods: The investigation carried out using the laboratory information management system. Forensic toxicological identification and quantitation were performed in autopsy samples, including heart blood, peripheral blood, liver, kidney, vitreous humor and etc. Gas chromatography/mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to analyze the drugs and poisons. Results: Forensic autopsies were performed on 9,674 cases in this period. Based on the autopsy reports, 699 cases (7.2%) were considered as unnatural deaths caused by fatal intoxication. The number of male deaths was higher than that of female deaths, with the age of 50-59 being the most common age group. Conclusion: Drugs comprised the largest number of deaths due to poison, followed by alcohol, agrochemicals, drug with alcohol, carbon monoxide, and cyanide, in that order. Zolpidem was the most frequently used drug in all drug-related intoxication cases.

• YAKHAK HOEJI
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• v.59 no.5
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• pp.230-234
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• 2015

This paper includes a review of 555 drug-facilitated sexual assault (DFSA) cases analyzed at the National Forensic Service (NFS), South Korea, between 2006 and 2012. The results of toxicological analyses of blood and urine samples were also reported, and furthermore the results were interpreted with respect to the number of drugs detected. The number of DFSA cases was highest during warmer summer months and the mean age of the victims was 25 years, with 48% being between 20 and 29 years. Accommodations or entertainment places were the most frequent place of the sexual assault (57%); and the assailant was a stranger in 72% of the DFSA cases. Drugs were identified in the blood or urine samples in 145 cases (26%) and sedative-hypnotics, such as benzodiazepines and zolpidem, were the most commonly detected, along with sedative antihistamines such as doxylamine and diphenhydramine. The frequent presence of sedative drugs in biological samples tends to implicate their use in chemical submission. However, interpreting the analytical results in terms of voluntary vs. surreptitious administration of drugs requires further detailed investigation and knowledge of the victim's health status and medication used at the time of event.

• YAKHAK HOEJI
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• v.57 no.2
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• pp.101-109
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• 2013

Depressive disorders are the most common psychiatric problem in the elderly. Most depression treatment guidelines emphasize treatment with antidepressant medication and recommend that benzodiazepine use be minimized for limited period, particularly to elderly patients. In order to evaluate appropriate use of antidepressants and benzodiazepine, retrospective review of prescriptions was performed. The study population are older than 65 years who had been newly diagnosed with major depressive disorder in specialty mental health at a community general hospital from January $1^{st}$, 2007 to October $31^{th}$, 2012 (N=373). Initial antidepressant accounted for 89.5% with SSRI, and escitalopram accounted for 60.9% of SSRI group. 79% or more of the patients were prescribed the recommended dosage. The maintenance rate for 4 weeks of initial antidepressant was 48% and 6 weeks was 39%. Treatment-discontinuation rate was 68% at 3 month. Alprazolam (short acting benzodiazepine) was prescribed the most, followed by clonazepam (long acting benzodiazepine) and then diazepam. 55% of patients received a duplicated prescription for short acting plus long acting benzodiazepine. 61% of patients used long acting benzodiazepines. Prescribed dosages of benzodiazepines were commonly within a recommended range, while no one was prescribed a appropriate period (up to 2 weeks) except for the early discontinued patients. Appropriate use of zolpidem was only 16.2%. The depressed elderly treated in specialty mental health mostly received long-term treatment with benzodiazepines in combination with antidepressants, guideline recommendations was not followed. Multidisciplinary interventions like audit and feedback of benzodiazepine use are needed and education for the elderly is needed to properly maintain antidepressant treatment.