Research Interests: Medicine, Norway, Humans, Smoking Cessation, Smoking, and 3 morePubmed, Serotonin Syndrome, and Paroxetine
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Alcohol abuse has significant medical, social and socioeconomic consequences. Alcohol biomarkers may serve as a useful tool in identifying individuals with excessive alcohol consumption in medical as well as medico-legal contexts.
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In this study we have evaluated the postmortem pharmacokinetics of amitriptyline (Ami) and metabolites in pigs after oral and intravenous administration, and the results are compared with previous studies in rats and humans. In addition a... more
In this study we have evaluated the postmortem pharmacokinetics of amitriptyline (Ami) and metabolites in pigs after oral and intravenous administration, and the results are compared with previous studies in rats and humans. In addition a meticulous investigation of blood and tissue concentrations after postmortem intravenous infusion of Ami was undertaken. Of a total of 9 over-night fasted pigs, 3 were given 25 mg/Kg Ami orally, and another 3 pigs received an intravenous infusion lasting 1 h of 3.3 mg/Kg Ami prior to death. The final 3 pigs were sacrificed and then given the intravenous infusion after death. After approximately 5 h at room temperature, all carcasses were subsequently stored at 4-5 degrees C. Postmortem blood samples were collected at 0.25, 1, 2, 4, 8, 24, 48, and 96 h through an indwelling intracardial needle. Postmortem examination with blood and tissue sampling was performed 96 h after death. Analysis was carried out by high performance liquid chromatography with ultraviolet detection. Postmortem blood samples from the heart of the orally dosed animals revealed large and variable concentration increases of 99(30-243)% for Ami and 96(52-429)% for the main metabolite 10-OH-Ami at 96 h. In the intravenously infused live pigs heart blood Ami increased by 55(33-69)% and 10-OH-Ami increased by 232(76-240)%. Blood from the atria had significantly higher Ami concentrations than blood from both ventricles in the animals dosed while alive, and the drug concentration in femoral blood was higher than in heart blood (p < 0.01). In the orally dosed pigs the left lobe of the liver had significantly higher Ami levels than the right lobe. Tissue/blood Ami concentration ratios were generally lower than previously reported in rats and approximating the levels reported in humans. The animals infused intravenously after death demonstrated high drug levels in blood samples from central vessels, heart, lungs as well as cerebrospinal fluid and vitreous humour. This implies that the presence of a lethal concentration of a drug in just one sample of heart blood can prove worthless in a case where agonal drug infusion may have occurred.
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Research Interests: Nepal, Adolescent, Medicine, Comorbidity, Humans, and 15 moreMajor Depressive Disorder, Alcohol, Alcoholism, Female, Male, Nutritional Status, Middle Aged, Adult, Inpatients, Cross sectional Study, Cross Sectional Studies, confounding, Psychology and Cognitive Sciences, Alcohol use disorder, and Medical and Health Sciences
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Research Interests: Forensic Science, Medicine, Multidisciplinary, Humans, Antidepressant, and 15 moreFemale, Animals, Male, Experimental Study, Middle Aged, Autopsy, Adult, Monoamine oxidase, Benzamides, Mortality rate, Cause of death, Drug synergism, monoamine oxidase inhibitor, Antidepressive agents, and Fatal outcome
The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs:... more
The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbamazepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemazine) or chloroquine was administered together with nortriptyline orally to rats 90 min prior to sacrifice. Heart blood was sampled immediately before sacrifice and after 2 h postmortem, as it has previously been shown that this is sufficient time for postmortem concentration changes to occur in heart blood. Blood was also sampled from the clamped abdominal inferior vena cava (representing peripheral blood) and tissue samples were taken from lungs, myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor together with a specimen from the minced carcass. Drugs were analyzed by high performance liquid or gas chromatography. For phenobarbital, acetaminophen and carbamazepine the postmortem to antemortem blood drug concentration ratios were close to 1.0 and tissue concentrations were low. The postmortem to antemortem heart blood drug concentration ratio for chloroquine (6.9 +/- 1.5) was higher than for nortriptyline (3.5 +/- 0.3), and the remaining drugs (codeine, verapamil, amphetamine, mianserin, and trimeprazine) showed ratios of the same magnitude as nortriptyline. The postmortem to antemortem blood drug concentration ratios for both heart blood and blood from the vena cava and also the lung to antemortem blood drug concentration ratio were closely related to the apparent volume of distribution for the drugs studied (p < 0.001). Accordingly, an apparent volume of distribution of more than 3-4 L/kg is a good predictor that a drug is liable to undergo postmortem redistribution with significant increments in blood levels. The postmortem drug concentration in blood from vena cava was closely related to the antemortem blood level, confirming that among the postmortem samples, the peripheral blood sample was the most representative for the antemortem blood concentration.
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This study is part of a prospective quality assurance project in a Norwegian county hospital. The major aims of the study were to estimate the number of drug-related deaths; assess whether these were recognized by the clinicians, and (if... more
This study is part of a prospective quality assurance project in a Norwegian county hospital. The major aims of the study were to estimate the number of drug-related deaths; assess whether these were recognized by the clinicians, and (if not) discuss why the clinicians had difficulties in recognizing drug-related deaths. A panel of two internists, one pathologist, one pharmacologist and one pharmacist evaluated all inpatients deaths over a six-month period. Among 3,082 hospitalized patients, 169 died. Of these deaths, 20 were classified as probably (nine) or possibility (11) drug-related. Only two of the deaths were recognized as such by the clinicians in the ward. The reasons for the clinicians failure to recognize adverse drug reactions include frequent presence of multiple diseases, polypharmacy and inadequate guidelines on how to look for adverse reactions to drugs. A two-year survey aimed at studying these aspects in depth is in progress.
Research Interests: Norwegian, Medicine, Norway, Prospective studies, Humans, and 15 moreDiuretics, Female, Poisoning, Male, Aged, Middle Aged, Adult, Combination drug therapy, Drug Reaction, Polypharmacy, Hospital Mortality, Angiotensin Converting Enzyme Inhibitors, Prospective Cohort Study, Cause of death, and Fatal outcome
In order to reach an estimate of drug-related deaths, the Adverse Drug Reaction Committee/the Norwegian Medicines Control Authority obtained access to data from the Department of Internal Medicine in a Norwegian county hospital. The... more
In order to reach an estimate of drug-related deaths, the Adverse Drug Reaction Committee/the Norwegian Medicines Control Authority obtained access to data from the Department of Internal Medicine in a Norwegian county hospital. The criteria for classifying possible/probable cause of drug-related deaths were assessed. 6.5 deaths per 1,000 hospitalized persons were found to be probably or possibly drug-related. This figure far exceeds the numbers reported in the literature (0.9-4.4 per 1,000 hospitalized). Only two cases were detected by the clinician, one of which was reported to the Adverse Drug Reaction Committee via the spontaneous reporting system. The current criteria for assessing drug-related causes of death appear to be inadequate.
Research Interests: Norwegian, Medicine, Drug, Norway, Humans, and 8 morePubmed, Poisoning, Aged, Middle Aged, Adult, Adverse Drug Reaction, Hospital Mortality, and Cause of death
BackgroundThe aim of this study was to evaluate the quantitative relation between common clinical chemical analyses and ethanol use, measured by a combination of the two alcohol markers phosphatidylethanol (PEth) and... more
BackgroundThe aim of this study was to evaluate the quantitative relation between common clinical chemical analyses and ethanol use, measured by a combination of the two alcohol markers phosphatidylethanol (PEth) and carbohydrate‐deficient transferrin (CDT).MethodsResults of PEth and CDT in whole blood and serum, respectively, were included, together with information on 10 different commonly measured clinical chemical analytes, as well as age and sex. PEth was analysed by UPC2‐MS/MS and CDT was measured by capillary electrophoresis.ResultsSamples from 4873 patients were included. The strongest relation to alcohol consumption as measured by PEth, when correcting for age and sex, was found for HDL‐C (standardized β = 0.472, p < 0.001), AST (standardized β = 0.372, p < 0.001), ferritin (standardized β = 0.332, p < 0.001) and GGT (standardized β = 0.325, p < 0.001). The relation to PEth was weak for total cholesterol, TG and ALP. No relation was found for Hb and LDL‐C.ConclusionsWhen using PEth as a marker for alcohol consumption, this study demonstrated the quantitative relation to commonly used test as AST or GGT, but also an important relation to ferritin or HDL‐C. In clinical practice, elevated levels of these clinical chemical analytes should initiate further work‐up on possibly harmful alcohol use.
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In some cases of drug overdose there is a reservoir of unabsorbed drug in the stomach and gut. Furthermore, agonal aspiration might establish a second reservoir in the lungs. Two experimental rat models were used to study if diffusion... more
In some cases of drug overdose there is a reservoir of unabsorbed drug in the stomach and gut. Furthermore, agonal aspiration might establish a second reservoir in the lungs. Two experimental rat models were used to study if diffusion from these reservoirs could contribute to the phenomenon of postmortem drug redistribution. Overnight fasted rats were sacrificed by CO2 and 75 mg of amitriptyline (AMI) was administered by a gastric tube. In the first series (n = 19), the tubes were removed after AMI administration. In the second series (n = 17), the trachea was ligated and cut prior to drug administration to prevent airways contamination. The rats were left at room temperature on their back for a period of 5, 10, 24, 48, 96 up to 192 h and samples of heart blood, blood from the inferior vena cava, tissue samples from heart, lungs, different liver lobes, kidney and psoas muscle were taken. In both series of rats we observed that as early as 5 h postmortem increasing concentrations of amitriptyline were found in the liver lobes lying closest to the stomach. In rats where the trachea was not ligated, drug contamination of the lungs also resulted in an increase in drug concentration within 5 h in heart blood and heart muscle. In rats where the trachea had been ligated, amitriptyline was found in the lungs after 96 h postmortem. The main metabolite nortriptyline was also detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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An experimental rat model was developed to study postmortem changes of drug concentration after an acute overdose. Overnight fasted rats were fed 75 mg of amitriptyline (AMI). Two h after dosing, the rats were anaesthetized and blood... more
An experimental rat model was developed to study postmortem changes of drug concentration after an acute overdose. Overnight fasted rats were fed 75 mg of amitriptyline (AMI). Two h after dosing, the rats were anaesthetized and blood samples were drawn from the femoral vein (peripheral blood--PB) and the heart (HB). The rats were sacrificed by CO2 and left at room temperature for either 0.1, 0.5, 1, 2, 5, 10, 24, 48, or 96 hours, when samples of heart blood, blood from the inferior vena cava (PB) and tissue samples from different liver lobes, heart, lungs, kidney, thigh muscle, and brain were taken. Samples were analyzed by high performance liquid chromatography. The AMI concentration in HB increased fairly rapidly within the first 2 h postmortem and from then the average ratio was 6.4 +/- 0.8 (mean +/- sem) (n = 31). In PB, the post/antemortem AMI concentration ratio followed an approximately exponential rise; at 2 h postmortem the ratio was 1.6 +/- 0.3 (n = 5), and at 96 h 55.1 +/- 23.8 (n = 4). For the main metabolite nortriptyline (NOR), the concentration changes followed the same pattern, but to a lesser extent. Among the tissues, the liver lobes had high, but variable drug concentrations; lobes lying closest to the stomach had the highest drug concentrations. The drug concentration in the lungs declined significantly. This animal model demonstrates postmortem drug concentration changes similar to those described in humans. Probable mechanisms include drug diffusion from the stomach and GI tract to the surrounding tissues and blood; and postmortem drug release from the lungs and possibly other drug-rich tissues into the blood.
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Femoral blood is widely accepted as the most reliable postmortem specimen for drug analysis in forensic toxicology. There is considerable evidence that the drug concentrations in peripheral blood samples are closer to the antemortem level... more
Femoral blood is widely accepted as the most reliable postmortem specimen for drug analysis in forensic toxicology. There is considerable evidence that the drug concentrations in peripheral blood samples are closer to the antemortem level than the concentration in cardiac blood. In the present study drug concentrations measured in postmortem femoral and/or heart blood samples from eight cases were compared with the concentration found in serum samples from the same subject collected antemortem or perimortem. The drugs involved were amitriptyline, nortriptyline, imipramine, verapamil and chloroquine. Two additional cases with very early postmortem blood samples, as well as femoral blood samples from later autopsy, involved amphetamine and tetrahydrocannabinol. The results from the human cases were compared with results from rat experiments on similar drugs. The samples were analyzed by high performance liquid or gas chromatography. The cases with tricyclic antidepressants had a median postmortern femoral blood to antemortem serum drug concentration ratio of 3.3, the 95% reference range being from 1.1 to 6.0 (pooled data). Large variations of the ratios were seen. The extremes noted were a postmortem femoral blood to antemortem serum drug concentration ratio of 0.9 in a case with nortriptyline and 49 in the case with chloroquine. The low ratio in the former case could be due to attempted resuscitation, while the high ratio in the latter case is probably due to the extremely high apparent volume of distribution and a high blood to plasma concentration ratio for chloroquine. Accordingly, it is dubious whether the drug concentration found in femoral blood at autopsy can be accepted as being representative for the antemortem level. The results obtained from the human cases in the present study were generally in reasonable agreement with previous rat experiments, confirming that the animal studies when interpreted carefully, are indicative of the changes observed in man as well as a previous study in pigs. Studies on drug concentrations in pigs are not necessarily more representative for the findings in humans than experiments with a smaller animal like the rat. The postmortem concentration changes observed for tetrahydrocannabinol in man were found to be unpredictable, while in the accompanying experimental rat study there was a significant postmortem decrease in the tetrahydrocannabinol blood concentration measured in blood from the inferior vena cava. In special cases where the diagnosis of overdose is to be used as judicial evidence, a single sample of blood may prove insufficient. In such cases, analyses of several samples of blood and tissue will increase the possibility of reaching a correct conclusion, but reference values on drug concentrations in tissues are often missing.
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BackgroundIn order to target the complex health needs of patients with multimorbidity using psychoactive substances, knowledge regarding the association between substance use and multimorbidity in an acute setting is needed.AimsExamine... more
BackgroundIn order to target the complex health needs of patients with multimorbidity using psychoactive substances, knowledge regarding the association between substance use and multimorbidity in an acute setting is needed.AimsExamine psychoactive substance use patterns among acute medically ill patients, and determine the association between multimorbidity and substance use, and psychological distress.DesignCross-sectional study.Setting and participants2874 acute medically ill patients admitted to a medical emergency department in Oslo, Norway.MeasurementsPrimary outcome: multimorbidity recorded by the presence of ≥2 International Classification of Diseases 10th revision—physical and/or mental health conditions per patient, extracted from medical records. Predictor variables: self-reported data on age, sex, occupational status, psychological distress (Hopkins Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4) and results from blood samples on psychoact...
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Alcohol abuse has significant medical, social and socioeconomic consequences. Alcohol biomarkers may serve as a useful tool in identifying individuals with excessive alcohol consumption in medical as well as medico-legal contexts.
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More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new... more
More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis. The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification. All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway. The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries.
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The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs:... more
The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbamazepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemazine) or chloroquine was administered together with nortriptyline orally to rats 90 min prior to sacrifice. Heart blood was sampled immediately before sacrifice and after 2 h postmortem, as it has previously been shown that this is sufficient time for postmortem concentration changes to occur in heart blood. Blood was also sampled from the clamped abdominal inferior vena cava (representing peripheral blood) and tissue samples were taken from lungs, myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor together with a specimen from the minced carcass. Drugs were analyzed by high performance liquid or...
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Femoral blood is widely accepted as the most reliable postmortem specimen for drug analysis in forensic toxicology. There is considerable evidence that the drug concentrations in peripheral blood samples are closer to the antemortem level... more
Femoral blood is widely accepted as the most reliable postmortem specimen for drug analysis in forensic toxicology. There is considerable evidence that the drug concentrations in peripheral blood samples are closer to the antemortem level than the concentration in cardiac blood. In the present study drug concentrations measured in postmortem femoral and/or heart blood samples from eight cases were compared with the concentration found in serum samples from the same subject collected antemortem or perimortem. The drugs involved were amitriptyline, nortriptyline, imipramine, verapamil and chloroquine. Two additional cases with very early postmortem blood samples, as well as femoral blood samples from later autopsy, involved amphetamine and tetrahydrocannabinol. The results from the human cases were compared with results from rat experiments on similar drugs. The samples were analyzed by high performance liquid or gas chromatography. The cases with tricyclic antidepressants had a media...
Research Interests: Pharmacokinetics, Forensic Medicine, Adolescent, Humans, Forensic Sciences, and 15 moreFemale, Animals, Male, Clinical Sciences, Middle Aged, Autopsy, Rats, Adult, Wistar Rats, Coronary Circulation, Gunshot wounds, Pharmaceutical preparations, Femoral Artery, Tissue distribution, and Blood Specimen Collection
In this study we have evaluated the postmortem pharmacokinetics of amitriptyline (Ami) and metabolites in pigs after oral and intravenous administration, and the results are compared with previous studies in rats and humans. In addition a... more
In this study we have evaluated the postmortem pharmacokinetics of amitriptyline (Ami) and metabolites in pigs after oral and intravenous administration, and the results are compared with previous studies in rats and humans. In addition a meticulous investigation of blood and tissue concentrations after postmortem intravenous infusion of Ami was undertaken. Of a total of 9 over-night fasted pigs, 3 were given 25 mg/Kg Ami orally, and another 3 pigs received an intravenous infusion lasting 1 h of 3.3 mg/Kg Ami prior to death. The final 3 pigs were sacrificed and then given the intravenous infusion after death. After approximately 5 h at room temperature, all carcasses were subsequently stored at 4-5 degrees C. Postmortem blood samples were collected at 0.25, 1, 2, 4, 8, 24, 48, and 96 h through an indwelling intracardial needle. Postmortem examination with blood and tissue sampling was performed 96 h after death. Analysis was carried out by high performance liquid chromatography with...
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An experimental rat model was developed to study postmortem changes of drug concentration after an acute overdose. Overnight fasted rats were fed 75 mg of amitriptyline (AMI). Two h after dosing, the rats were anaesthetized and blood... more
An experimental rat model was developed to study postmortem changes of drug concentration after an acute overdose. Overnight fasted rats were fed 75 mg of amitriptyline (AMI). Two h after dosing, the rats were anaesthetized and blood samples were drawn from the femoral vein (peripheral blood--PB) and the heart (HB). The rats were sacrificed by CO2 and left at room temperature for either 0.1, 0.5, 1, 2, 5, 10, 24, 48, or 96 hours, when samples of heart blood, blood from the inferior vena cava (PB) and tissue samples from different liver lobes, heart, lungs, kidney, thigh muscle, and brain were taken. Samples were analyzed by high performance liquid chromatography. The AMI concentration in HB increased fairly rapidly within the first 2 h postmortem and from then the average ratio was 6.4 +/- 0.8 (mean +/- sem) (n = 31). In PB, the post/antemortem AMI concentration ratio followed an approximately exponential rise; at 2 h postmortem the ratio was 1.6 +/- 0.3 (n = 5), and at 96 h 55.1 +/...
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In order to reach an estimate of drug-related deaths, the Adverse Drug Reaction Committee/the Norwegian Medicines Control Authority obtained access to data from the Department of Internal Medicine in a Norwegian county hospital. The... more
In order to reach an estimate of drug-related deaths, the Adverse Drug Reaction Committee/the Norwegian Medicines Control Authority obtained access to data from the Department of Internal Medicine in a Norwegian county hospital. The criteria for classifying possible/probable cause of drug-related deaths were assessed. 6.5 deaths per 1,000 hospitalized persons were found to be probably or possibly drug-related. This figure far exceeds the numbers reported in the literature (0.9-4.4 per 1,000 hospitalized). Only two cases were detected by the clinician, one of which was reported to the Adverse Drug Reaction Committee via the spontaneous reporting system. The current criteria for assessing drug-related causes of death appear to be inadequate.
Research Interests: Norway, Humans, Poisoning, Aged, Middle Aged, and 3 moreAdult, Hospital Mortality, and Cause of death
This study is part of a prospective quality assurance project in a Norwegian county hospital. The major aims of the study were to estimate the number of drug-related deaths; assess whether these were recognized by the clinicians, and (if... more
This study is part of a prospective quality assurance project in a Norwegian county hospital. The major aims of the study were to estimate the number of drug-related deaths; assess whether these were recognized by the clinicians, and (if not) discuss why the clinicians had difficulties in recognizing drug-related deaths. A panel of two internists, one pathologist, one pharmacologist and one pharmacist evaluated all inpatients deaths over a six-month period. Among 3,082 hospitalized patients, 169 died. Of these deaths, 20 were classified as probably (nine) or possibility (11) drug-related. Only two of the deaths were recognized as such by the clinicians in the ward. The reasons for the clinicians failure to recognize adverse drug reactions include frequent presence of multiple diseases, polypharmacy and inadequate guidelines on how to look for adverse reactions to drugs. A two-year survey aimed at studying these aspects in depth is in progress.
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The death of a 72-year-old woman with respiratory debilitation due to bronchogenic carcinoma is described. She overdosed herself with probably 200 to 350 mg of zopiclone. Zopiclone, quantitated by HPLC in femoral postmortem blood, was... more
The death of a 72-year-old woman with respiratory debilitation due to bronchogenic carcinoma is described. She overdosed herself with probably 200 to 350 mg of zopiclone. Zopiclone, quantitated by HPLC in femoral postmortem blood, was found to be 1.9 mg/L (4.8 micromol/L). This level is higher than many other zopiclone fatalities reported. We report a case where only zopiclone was detected.