Postmortem Femoral Blood Reference Concentrations of Aripiprazole, Chlorprothixene, and Quetiapine

DEFF Research Database (Denmark)

Skov, Louise; Johansen, Sys Stybe; Linnet, Kristian

2015-01-01

no or only limited postmortem redistribution for aripiprazole, chlorprothixene with metabolite, and quetiapine in these cases. One fatality caused by chlorprothixene with a blood level of 0.90 mg/kg was recorded, and in six cases chlorprothixene was judged to be contributing to death with concentrations 0...

Segmental Analysis of Chlorprothixene and Desmethylchlorprothixene in Postmortem Hair.

Science.gov (United States)

Günther, Kamilla Nyborg; Johansen, Sys Stybe; Wicktor, Petra; Banner, Jytte; Linnet, Kristian

2018-06-26

Analysis of drugs in hair differs from their analysis in other tissues due to the extended detection window, as well as the opportunity that segmental hair analysis offers for the detection of changes in drug intake over time. The antipsychotic drug chlorprothixene is widely used, but few reports exist on chlorprothixene concentrations in hair. In this study, we analyzed hair segments from 20 deceased psychiatric patients who had undergone chronic chlorprothixene treatment, and we report hair concentrations of chlorprothixene and its metabolite desmethylchlorprothixene. Three to six 1-cm long segments were analyzed per individual, corresponding to ~3-6 months of hair growth before death, depending on the length of the hair. We used a previously published and fully validated liquid chromatography-tandem mass spectrometry method for the hair analysis. The 10th-90th percentiles of chlorprothixene and desmethylchlorprothixene concentrations in all hair segments were 0.05-0.84 ng/mg and 0.06-0.89 ng/mg, respectively, with medians of 0.21 and 0.24 ng/mg, and means of 0.38 and 0.43 ng/mg. The estimated daily dosages ranged from 28 mg/day to 417 mg/day. We found a significant positive correlation between the concentration in hair and the estimated daily doses for both chlorprothixene (P = 0.0016, slope = 0.0044 [ng/mg hair]/[mg/day]) and the metabolite desmethylchlorprothixene (P = 0.0074). Concentrations generally decreased throughout the hair shaft from proximal to distal segments, with an average reduction in concentration from segment 1 to segment 3 of 24% for all cases, indicating that most of the individuals had been compliant with their treatment. We have provided some guidance regarding reference levels for chlorprothixene and desmethylchlorprothixene concentrations in hair from patients undergoing long-term chlorprothixene treatment.

Chemical Genetic Screens for TDP-43 Modifiers and ALS Drug Discovery

Science.gov (United States)

2013-10-01

red. Chlo= Chlorprothixene hydrochloride; Amo= Amoxapine; Mians = Mianserine hydrochloride; Pizo= Pizotifen malate; Pimet= Pimethixene maleate; Cloz...lobar degeneration in transgenic mice produced with TDP-43 genomic fragments. Brain. 32. Li Y, Ray P, Rao EJ, Shi C, Guo W, et al. (2010) A Drosophila...2008) Sirtuin Inhibition Protects from the Polyalanine Muscular Dystrophy Protein PABPN1. Hum Mol Genet. 36. Wang J, Farr GW, Hall DH, Li F, Furtak

Association of Selected Antipsychotic Agents With Major Adverse Cardiovascular Events and Noncardiovascular Mortality in Elderly Persons

DEFF Research Database (Denmark)

Sahlberg, Marie; Holm, Ellen; Gislason, Gunnar H

2015-01-01

events and noncardiovascular mortality associated with individual APs (ziprasidone, olanzapine, risperidone, quetiapine, levomepromazine, chlorprothixen, flupentixol, and haloperidol) in Danish treatment-naïve patients aged ≥70 years. METHODS AND RESULTS: We followed all treatment-naïve Danish citizens...... of treatment, compared with risperidone, incidence rate ratios of major adverse cardiovascular events were higher with use of levomepromazine (3.80, 95% CI 3.43 to 4.21) and haloperidol (1.85, 95% CI 1.67 to 2.05) and lower for treatment with flupentixol (0.54, 95% CI 0.45 to 0.66), ziprasidone (0.31, 95% CI 0...

Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period

DEFF Research Database (Denmark)

Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose

2018-01-01

analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology......Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug......-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid...

Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period.

Science.gov (United States)

Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose; Linnet, Kristian

2018-04-01

Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology. A literature review on concentrations in the published DFC-related hair cases and on concentrations in hair of these substances after single and multiple doses is included. These cases demonstrate the value of segmental hair analysis in DFCs and facilitate future interpretations of results. Copyright © 2018 Elsevier B.V. All rights reserved.

Zuclopenthixol dihydrochloride for schizophrenia.

Science.gov (United States)

Bryan, Edward J; Purcell, Marie Ann; Kumar, Ajit

2017-11-16

the outcomes of global state (average CGI-SI endpoint score) (1 RCT, n = 60, MD 0.00, 95% CI -0.49 to 0.49) or movement disorders (EPSEs) (3 RCTs, n = 199, RR 0.94, 95% CI 0.61 to 1.45), both very low-quality evidence. More people left the study early for any reason from the zuclopenthixol group (6 RCTs, n = 766, RR 0.54, 95% CI 0.36 to 0.81, low-quality evidence). 3. chlorprothixeneThere was no clear difference in numbers leaving the study early for any reason (1 RCT, n = 20, RR 1.00, 95% CI 0.34 to 2.93, very low-quality evidence). 4. clozapineNo useable data were presented. 5. haloperidolNo clear differences between treatment groups were found for the outcomes global state score (average CGI endpoint score) (1 RCT, n = 49, MD 0.13, 95% CI -0.30 to 0.55) or leaving the study early (2 RCTs, n = 141, RR 0.99, 95% CI 0.72 to 1.35), both very low-quality evidence. 6. perphenazineThose receiving zuclopenthixol were more likely to require medication in the short term for EPSEs than perphenazine (1 RCT, n = 50, RR 1.90, 95% CI 1.12 to 3.22, very low-quality evidence). Similar numbers left the study early (2 RCTs, n = 104, RR 0.63, 95% CI 0.27 to 1.47, very low-quality evidence). 7. risperidoneThose receiving zuclopenthixol were more likely to require medications for EPSEs than risperidone (1 RCT, n = 98,RR 1.92, 95% CI 1.12 to 3.28, very low quality evidence). There was no clear difference in numbers leaving the study early ( 3 RCTs, n = 154, RR 1.30, 95% CI 0.84 to 2.02) or in mental state (average PANSS total endpoint score) (1 RCT, n = 25, MD -3.20, 95% CI -7.71 to 1.31), both very low-quality evidence). 8. sulpirideNo clear differences were found for global state (average CGI endpoint score) ( 1 RCT, n = 61, RR 1.18, 95% CI 0.49 to 2.85, very low-quality evidence), requiring hypnotics/sedatives (1 RCT, n = 61, RR 0.60, 95% CI 0.27 to 1.32, very low-quality evidence) or leaving the study early (1 RCT, n = 61, RR 2.07 95% CI 0.97 to 4.40, very low-quality evidence). 9