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[PMID]:28242100
[Au] Autor:Sacre L; Ali SM; Villa A; Jouffroy R; Raphalen JH; Garnier R; Baud FJ
[Ad] Endereço:UMR 8257 cognitive action group, Paris Descartes university, 45, rue des Saints-Pères, 75270 Paris cedex 06, France; Paris poison control centre, hôpital Fernand-Widal, 200, rue du Faubourg-Saint-Denis, 75010 Paris, France. Electronic address: lynnsacre@hotmail.com.
[Ti] Título:Toxicodynetics in nordiazepam and oxazepam overdoses.
[So] Source:Ann Pharm Fr;75(3):163-171, 2017 May.
[Is] ISSN:0003-4509
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Toxicodynetics aims at defining the time-course of major clinical events in drug overdose. We report the toxicodynetics in mono-intoxications with oxazepam and nordiazepam. METHODS: Cases of oxazepam or nordiazepam overdoses collected at the Paris poison control centre from 1999 to 2014 on the basis of self-report. A particular attention was paid to eliminate the concomitant alcohol or psychotropic co-ingestions. The toxicodynetic parameters were assessed as previously described. Results are expressed using 10-90 percentiles. In adults, the dose was normalized (TI, toxic Index) by dividing the supposed ingested dose by the maximal recommended dose. RESULTS: Two hundred and fifty-one and 74 cases of oxazepam and nordiazepam poisonings were included, respectively. The Emax for oxazepam and nordiazepam were sleepiness or obtundation in 106 and 36 cases, respectively. Coma was used to qualify only one oxazepam overdose. The median delay in onset of the Emax was 1.5h (0.33-15) in nordiazepam and 4h (0.5-15) in oxazepam overdose. In both overdoses, the onset of Emax occurred on an "on-off" mode. In adults, the greatest TIs in nordiazepam and oxazepam overdoses were 45 and 26.7, respectively. The TI in the oxazepam-induced coma was 26.7, the largest dose. CONCLUSION: Data collected in PCC allow determining a number of toxicodynetic parameters. Toxicodynetics showed that nordiazepam is not a cause of coma even in large overdose while oxazepam causes coma only at a very high dose. Deep coma in nordiazepam overdose whatever the dose and deep coma in overdose with oxazepam involving TI less than 20 result from unrecognized drug-drug interaction.
[Mh] Termos MeSH primário: Overdose de Drogas/metabolismo
Moduladores GABAérgicos/efeitos adversos
Moduladores GABAérgicos/farmacocinética
Nordazepam/efeitos adversos
Nordazepam/farmacocinética
Oxazepam/efeitos adversos
Oxazepam/farmacocinética
Toxicocinética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Envelhecimento/metabolismo
Depressores do Sistema Nervoso Central/efeitos adversos
Criança
Pré-Escolar
Etanol/efeitos adversos
Feminino
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Central Nervous System Depressants); 0 (GABA Modulators); 3K9958V90M (Ethanol); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170301
[St] Status:MEDLINE


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[PMID]:27534563
[Au] Autor:Wang X; Johansen SS; Zhang Y; Jia J; Rao Y; Jiang F; Linnet K
[Ad] Endereço:Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Frederik V's Vej 11, 2100, Copenhagen, Denmark. xinwangyao@163.com.
[Ti] Título:Deposition of diazepam and its metabolites in hair following a single dose of diazepam.
[So] Source:Int J Legal Med;131(1):131-141, 2017 Jan.
[Is] ISSN:1437-1596
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide and temazepam glucuronide, were measured by ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with limits of quantifications (LOQs) of 0.5-2.5 pg/mg for diazepam, nordazepam, oxazepam, and temazepam, and of 10 pg/mg for oxazepam glucuronide and temazepam glucuronide. There were no differences by gender in the amounts of diazepam or metabolites found. The concentration of the main metabolite nordazepam was consistently higher than that of diazepam at both 1 and 2 months after consumption. Oxazepam and temazepam traces were found in some volunteers' hair, but the glucuronides were not detected. Diazepam and nordazepam levels at 10 months post-exposure were extremely low (near the LOQ), indicating drug loss by personal hygiene and physical handling. To our knowledge, this is the first single-dose diazepam study using black hair and the first study to include measurements of oxazepam glucuronide and temazepam glucuronide in human hair.
[Mh] Termos MeSH primário: Diazepam/análise
Cabelo/química
Hipnóticos e Sedativos/análise
[Mh] Termos MeSH secundário: Adulto
Grupo com Ancestrais do Continente Asiático
Cromatografia Líquida
Diazepam/administração & dosagem
Feminino
Voluntários Saudáveis
Seres Humanos
Hipnóticos e Sedativos/administração & dosagem
Masculino
Nordazepam/análise
Oxazepam/análogos & derivados
Oxazepam/análise
Espectrometria de Massas em Tandem
Temazepam/análogos & derivados
Temazepam/análise
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 26IK2C76NO (oxazepam glucuronide); 3703-53-5 (temazepam glucuronide); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160819
[St] Status:MEDLINE
[do] DOI:10.1007/s00414-016-1429-x


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[PMID]:26970544
[Au] Autor:Nakayama SM; Ikenaka Y; Hayami A; Mizukawa H; Darwish WS; Watanabe KP; Kawai YK; Ishizuka M
[Ad] Endereço:Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, Sapporo, Japan.
[Ti] Título:Characterization of equine cytochrome P450: role of CYP3A in the metabolism of diazepam.
[So] Source:J Vet Pharmacol Ther;39(5):478-87, 2016 Oct.
[Is] ISSN:1365-2885
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Research on drug metabolism and pharmacokinetics in large animal species including the horse is scarce because of the challenges in conducting in vivo studies. The metabolic reactions catalyzed by cytochrome P450s (CYPs) are central to drug pharmacokinetics. This study elucidated the characteristics of equine CYPs using diazepam (DZP) as a model compound as this drug is widely used as an anesthetic and sedative in horses, and is principally metabolized by CYPs. Diazepam metabolic activities were measured in vitro using horse and rat liver microsomes to clarify the species differences in enzyme kinetic parameters of each metabolite (temazepam [TMZ], nordiazepam [NDZ], p-hydroxydiazepam [p-OH-DZP], and oxazepam [OXZ]). In both species microsomes, TMZ was the major metabolite, but the formation rate of p-OH-DZP was significantly less in the horse. Inhibition assays with a CYP-specific inhibitors and antibody suggested that CYP3A was the main enzyme responsible for DZP metabolism in horse. Four recombinant equine CYP3A isoforms expressed in Cos-7 cells showed that CYP3A96, CYP3A94, and CYP3A89 were important for TMZ formation, whereas CYP3A97 exhibited more limited activity. Phylogenetic analysis suggested diversification of CYP3As in each mammalian order. Further study is needed to elucidate functional characteristics of each equine CYP3A isoform for effective use of diazepam in horses.
[Mh] Termos MeSH primário: Citocromo P-450 CYP3A/metabolismo
Diazepam/farmacocinética
Cavalos/metabolismo
Hipnóticos e Sedativos/farmacocinética
[Mh] Termos MeSH secundário: Animais
Células COS/enzimologia
Células COS/metabolismo
Cercopithecus aethiops
Citocromo P-450 CYP3A/genética
Diazepam/análogos & derivados
Masculino
Microssomos Hepáticos/enzimologia
Microssomos Hepáticos/metabolismo
Nordazepam/farmacocinética
Oxazepam/farmacocinética
Filogenia
Isoformas de Proteínas/metabolismo
Ratos
Ratos Sprague-Dawley
Especificidade da Espécie
Temazepam/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 0 (Protein Isoforms); 17311-35-2 (4'-hydroxydiazepam); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam); EC 1.14.14.1 (Cytochrome P-450 CYP3A); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170623
[Lr] Data última revisão:
170623
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160313
[St] Status:MEDLINE
[do] DOI:10.1111/jvp.12303


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[PMID]:26840622
[Au] Autor:Torabizadeh M; Talebpour Z; Adib N; Aboul-Enein HY
[Ad] Endereço:Department of Chemistry, Faculty of Physics & Chemistry, University of Alzahra, Vanak, Tehran, Iran.
[Ti] Título:Preparation of a novel sorptive stir bar based on vinylpyrrolidone-ethylene glycol dimethacrylate monolithic polymer for the simultaneous extraction of diazepam and nordazepam from human plasma.
[So] Source:J Sep Sci;39(7):1316-25, 2016 Apr.
[Is] ISSN:1615-9314
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A new monolithic coating based on vinylpyrrolidone-ethylene glycol dimethacrylate polymer was introduced for stir bar sorptive extraction. The polymerization step was performed using different contents of monomer, cross-linker and porogenic solvent, and the best formulation was selected. The quality of the prepared vinylpyrrolidone-ethylene glycol dimethacrylate stir bars was satisfactory, demonstrating good repeatability within batch (relative standard deviation < 3.5%) and acceptable reproducibility between batches (relative standard deviation < 6.0%). The prepared stir bar was utilized in combination with ultrasound-assisted liquid desorption, followed by high-performance liquid chromatography with ultraviolet detection for the simultaneous determination of diazepam and nordazepam in human plasma samples. To optimize the extraction step, a three-level, four-factor, three-block Box-Behnken design was applied. Under the optimum conditions, the analytical performance of the proposed method displayed excellent linear dynamic ranges for diazepam (36-1200 ng/mL) and nordazepam (25-1200 ng/mL), with correlation coefficients of 0.9986 and 0.9968 and detection limits of 12 and 10 ng/mL, respectively. The intra- and interday recovery ranged from 93 to 106%, and the relative standard deviations were less than 6%. Finally, the proposed method was successfully applied to the analysis of diazepam and nordazepam at their therapeutic levels in human plasma. The novelty of this study is the improved polarity of the stir bar coating and its application for the simultaneous extraction of diazepam and its active metabolite, nordazepam in human plasma sample. The method was more rapid than previously reported stir bar sorptive extraction techniques based on monolithic coatings, and exhibited lower detection limits in comparison with similar methods for the determination of diazepam and nordazepam in biological fluids.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/instrumentação
Diazepam/sangue
Diazepam/isolamento & purificação
Metacrilatos/química
Nordazepam/sangue
Nordazepam/isolamento & purificação
Pirrolidinonas/química
[Mh] Termos MeSH secundário: Adsorção
Seres Humanos
Polimerização
Propriedades de Superfície
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Methacrylates); 0 (Pyrrolidinones); 67220MCM01 (Nordazepam); 7BK5G69305 (ethylene dimethacrylate); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160204
[St] Status:MEDLINE
[do] DOI:10.1002/jssc.201501273


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[PMID]:25652266
[Au] Autor:Li J; Zhang J; Liu H; Wu L
[Ad] Endereço:Chinese Academy of Fishery Sciences, Quality and Standard Research Center, Beijing 100141, People's Republic of China.
[Ti] Título:A comparative study of primary secondary amino (PSA) and multi-walled carbon nanotubes (MWCNTs) as QuEChERS absorbents for the rapid determination of diazepam and its major metabolites in fish samples by high-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry.
[So] Source:J Sci Food Agric;96(2):555-60, 2016 Jan 30.
[Is] ISSN:1097-0010
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A simple and fast modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method is presented for the determination of diazepam and its three major metabolites, nordiazepam, temazepam and oxazepam (benzodiazepines) in fish samples by liquid chromatography-electrospray ionisation-tandem mass spectrometry. RESULTS: Muscle tissues were extracted with acetonitrile, and then cleaned with primary secondary amino (PSA) adsorbents. The cleanup effect of PSA was compared with that of multi-walled carbon nanotubes (MWCNTs) in term of extraction efficiency. The better results were obtained when PSA was used. The chromatography separation was achieved within 5.0 min on a C18 column. The limit of detection was 0.5 µg kg(-1) and the limit of quantification was 2.5 µg kg(-1). Average recoveries of diazepam and its main metabolites were in the range of 88.5-110.1%, with a relative standard deviation lower than 10.0%. CONCLUSION: The proposed method for fish samples gives good recoveries, linearity, precision and accuracy.
[Mh] Termos MeSH primário: Diazepam/análise
Peixes
Contaminação de Alimentos/análise
Nanotubos de Carbono/química
Alimentos Marinhos/análise
[Mh] Termos MeSH secundário: Adsorção
Animais
Cromatografia Líquida de Alta Pressão/métodos
Diazepam/metabolismo
Nordazepam/análise
Oxazepam/análise
Sensibilidade e Especificidade
Espectrometria de Massas por Ionização por Electrospray/métodos
Espectrometria de Massas em Tandem/métodos
Temazepam/análise
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nanotubes, Carbon); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:151223
[Lr] Data última revisão:
151223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150206
[St] Status:MEDLINE
[do] DOI:10.1002/jsfa.7123


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[PMID]:25458535
[Au] Autor:Klein S; Bankstahl M; Gramer M; Hausknecht M; Löscher W
[Ad] Endereço:Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
[Ti] Título:Low doses of ethanol markedly potentiate the anti-seizure effect of diazepam in a mouse model of difficult-to-treat focal seizures.
[So] Source:Epilepsy Res;108(10):1719-27, 2014 Dec.
[Is] ISSN:1872-6844
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Ethanol is commonly used as a solvent in injectable formulations of poorly water-soluble drugs. The concentrations of ethanol in such formulations are generally considered reasonably safe. It is long known that ethanol can potentiate central effects of sedatives and tranquillizers, particularly the benzodiazepines, most likely as a result of a synergistic interaction at the GABAA receptor. However, whether this occurs at the low systemic doses of ethanol resulting from its use as solvent in parenteral formulations of benzodiazepines is not known. In the present study we evaluated whether a commercial ethanol-containing aqueous solution of diazepam exerts more potent anti-seizure effects than an aqueous solution of diazepam hydrochloride or an aqueous emulsion of this drug in the intrahippocampal kainate model of temporal lobe epilepsy in mice. Spontaneous epileptic seizures in this model are known to be resistant to major antiepileptic drugs. Administration of the ethanol-containing formulation of diazepam caused an almost complete suppression of seizures. This was not seen when the same dose (5 mg/kg) of diazepam was administered as aqueous solution or emulsion, although all three diazepam formulations resulted in similar drug and metabolite concentrations in plasma. Our data demonstrate that ethanol-containing solutions of diazepam are superior to block difficult-to-treat seizures to other formulations of diazepam. To our knowledge, this has not been demonstrated before and, if this finding can be translated to humans, may have important consequences for emergency treatment of acute seizures, series of seizures, and initial treatment of status epilepticus in patients.
[Mh] Termos MeSH primário: Anticonvulsivantes/administração & dosagem
Diazepam/administração & dosagem
Etanol
Convulsões/tratamento farmacológico
Solventes
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/sangue
Anticonvulsivantes/química
Encéfalo/efeitos dos fármacos
Encéfalo/fisiopatologia
Diazepam/sangue
Diazepam/química
Modelos Animais de Doenças
Composição de Medicamentos
Sinergismo Farmacológico
Eletroencefalografia
Epilepsia do Lobo Temporal/tratamento farmacológico
Epilepsia do Lobo Temporal/fisiopatologia
Etanol/administração & dosagem
Etanol/sangue
Feminino
Ácido Caínico
Camundongos
Nordazepam/sangue
Oxazepam/sangue
Convulsões/fisiopatologia
Solventes/química
Solventes/farmacocinética
Temazepam/sangue
Água/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Solvents); 059QF0KO0R (Water); 3K9958V90M (Ethanol); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam); Q3JTX2Q7TU (Diazepam); SIV03811UC (Kainic Acid)
[Em] Mês de entrada:1508
[Cu] Atualização por classe:141209
[Lr] Data última revisão:
141209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141203
[St] Status:MEDLINE


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[PMID]:25199615
[Au] Autor:Bertol E; Mari F; Boscolo Berto R; Mannaioni G; Vaiano F; Favretto D
[Ad] Endereço:Department of Health Sciences, Forensic Toxicology Unit, University of Firenze, Italy.
[Ti] Título:A mixed MDPV and benzodiazepine intoxication in a chronic drug abuser: determination of MDPV metabolites by LC-HRMS and discussion of the case.
[So] Source:Forensic Sci Int;243:149-55, 2014 Oct.
[Is] ISSN:1872-6283
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:We report on a case of repeated MDPV consumptions that resulted in severe psychosis and agitation prompting the concomitant abuse of benzodiazepines. A 27-year-old man was found irresponsive in his apartment and was brought to the emergency department (ED) of a local hospital. When in ED, he rapidly recovered and self-reported to have recently injected some doses of MDPV that he had bought in the Internet. He left the hospital without medical cares. 15 days after, he was again admitted to the same ED due to severe agitation, delirium and hallucinations, and reported the use of MDPV and pharmaceutical drugs during the preceding week. He was sedated with diazepam and chlorpromazine. Urine samples collected in both occasions were sent for testing using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and liquid chromatography-high resolution multiple mass spectrometry (LC-HRMS/MS) on an Orbitrap. The LC-HRMS analysis revealed the presence of MDPV and its phase I and phase II metabolites (demethylenyl-MDPV, demethylenyl-methyl-MDPV, demethylenyl-methyl-oxo-MDPV, demethylenyl-hydroxy-alkyl-MDPV, demethylenyl-methyl-hydroxy alkyl-MDPV, demethylenyl-oxo-MDPV and their corresponding glucuronides), alprazolam and alprazolam metabolite at the first ED admission; at the time of the second ED access, the same MDPV metabolites, alprazolam, temazepam, and chlordiazepoxide were detected together with diazepam and metabolites. LC-HRMS/MS was use to determine the following concentrations, respectively on his first and second admission: MDPV 55ng/mL, alprazolam 114ng/mL, α-hydroxyalprazolam 104ng/mL; MDPV 35ng/mL, alprazolam 10.4ng/mL, α -hydroxyalprazolam 13ng/mL; chlordiazepoxide 13ng/mL, temazepam 170ng/mL, diazepam 1.3ng/mL, nordiazepam 61.5, oxazepam 115ng/mL. The toxicological findings corroborated the referred concomitant use of multiple pharmaceutical drugs and benzodiazepines. Confirmation of previous hypothesis on human metabolism of MDPV could be inferred by the analysis of urine.
[Mh] Termos MeSH primário: Benzodiazepinas/urina
Benzodioxóis/urina
Psicotrópicos/urina
Pirrolidinas/urina
[Mh] Termos MeSH secundário: Adulto
Alprazolam/análogos & derivados
Alprazolam/urina
Clordiazepóxido/urina
Cromatografia Líquida
Diazepam/urina
Seres Humanos
Hipnóticos e Sedativos/urina
Masculino
Espectrometria de Massas/métodos
Nordazepam/urina
Oxazepam/urina
Transtornos Relacionados ao Uso de Substâncias/urina
Temazepam/urina
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3,4-methylenedioxypyrovalerone); 0 (Benzodioxoles); 0 (Hypnotics and Sedatives); 0 (Psychotropic Drugs); 0 (Pyrrolidines); 12794-10-4 (Benzodiazepines); 37115-43-8 (alpha-hydroxyalprazolam); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); 6RZ6XEZ3CR (Chlordiazepoxide); CHB1QD2QSS (Temazepam); Q3JTX2Q7TU (Diazepam); YU55MQ3IZY (Alprazolam)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:141004
[Lr] Data última revisão:
141004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140910
[St] Status:MEDLINE


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[PMID]:25015743
[Au] Autor:Karinen R; Andresen W; Smith-Kielland A; Mørland J
[Ad] Endereço:Division of Forensic Sciences, Norwegian Institute of Public Health, PO Box 4404, Nydalen 0403, Oslo, Norway ritva.karinen@fhi.no.
[Ti] Título:Long-term storage of authentic postmortem forensic blood samples at -20°C: measured concentrations of benzodiazepines, central stimulants, opioids and certain medicinal drugs before and after storage for 16-18 years.
[So] Source:J Anal Toxicol;38(9):686-95, 2014 Nov-Dec.
[Is] ISSN:1945-2403
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The long-term stability of benzodiazepines, opioids, central stimulants and medicinal drugs in authentic postmortem blood samples was studied. All together, 73 samples were reanalyzed after storage at -20°C for 16-18 years. At reanalysis samples containing diazepam, nordiazepam and flunitrazepam demonstrated only small changes during long-term storage when mean and median drug concentrations were compared, while clonazepam concentrations tended to decrease. Samples containing amphetamine, morphine, codeine and 'acidic' medicinal drugs as paracetamol and meprobamate also showed small changes over 16-18 years in mean and median drug concentrations at a group level. For many drugs, however, single samples could demonstrate marked concentration changes, both increases and decreases during storage. For 'alkaline' medicinal drugs, concentration losses were observed in most cases.
[Mh] Termos MeSH primário: Analgésicos Opioides/sangue
Benzodiazepinas/sangue
Preservação de Sangue/métodos
Estimulantes do Sistema Nervoso Central/sangue
[Mh] Termos MeSH secundário: Anfetamina/sangue
Anfetamina/química
Analgésicos Opioides/química
Benzodiazepinas/química
Estimulantes do Sistema Nervoso Central/química
Codeína/sangue
Codeína/química
Diazepam/sangue
Diazepam/química
Flunitrazepam/sangue
Flunitrazepam/química
Toxicologia Forense/métodos
Congelamento
Seres Humanos
Morfina/sangue
Morfina/química
Nordazepam/sangue
Nordazepam/química
Detecção do Abuso de Substâncias/métodos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Central Nervous System Stimulants); 12794-10-4 (Benzodiazepines); 620X0222FQ (Flunitrazepam); 67220MCM01 (Nordazepam); 76I7G6D29C (Morphine); CK833KGX7E (Amphetamine); Q3JTX2Q7TU (Diazepam); Q830PW7520 (Codeine)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:141029
[Lr] Data última revisão:
141029
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140713
[St] Status:MEDLINE
[do] DOI:10.1093/jat/bku080


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[PMID]:24500275
[Au] Autor:Luk S; Atayee RS; Ma JD; Best BM
[Ad] Endereço:1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego (UC San Diego), 9500 Gilman Drive, MC 0719, La Jolla, CA, USA.
[Ti] Título:Urinary diazepam metabolite distribution in a chronic pain population.
[So] Source:J Anal Toxicol;38(3):135-42, 2014 Apr.
[Is] ISSN:1945-2403
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Diazepam is often used as an adjuvant to pain therapy. Cytochrome P450 (CYP) 3A4 and 2C19 metabolize diazepam into the active metabolites: nordiazepam, temazepam and oxazepam. Owing to diazepam's side-effect profile, mortality risk and potential for drug-drug interactions with CYP 3A4 and/or CYP 2C19 inhibitors, urine drug testing (UDT) could be a helpful monitoring tool. This was a retrospective data analysis that evaluated urine specimens from pain management practices for the distribution of diazepam metabolites with and without CYP 3A4 and 2C19 inhibitors. Intersubject nordiazepam, temazepam and oxazepam geometric mean fractions were 0.16, 0.34 and 0.47, respectively. Intrasubject geometric mean fractions were 0.157, 0.311 and 0.494, respectively. Sex, but not age or urinary pH, had an effect on metabolite fractions. Methadone significantly increased temazepam and oxazepam urinary fractions via CYP3A4 inhibition, whereas fluoxetine and esomeprazole increased nordiazepam fractions via CYP2C19 inhibition. Although more studies are needed, these results suggest the viability of UDT for increased monitoring for therapy and possible drug-drug interactions.
[Mh] Termos MeSH primário: Dor Crônica/tratamento farmacológico
Diazepam/administração & dosagem
Diazepam/urina
[Mh] Termos MeSH secundário: Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores
Hidrocarboneto de Aril Hidroxilases/metabolismo
Cromatografia Líquida de Alta Pressão
Dor Crônica/urina
Citocromo P-450 CYP2C19
Citocromo P-450 CYP3A/metabolismo
Inibidores do Citocromo P-450 CYP3A
Diazepam/efeitos adversos
Interações Medicamentosas
Esomeprazol/administração & dosagem
Feminino
Fluoxetina/administração & dosagem
Seres Humanos
Masculino
Metadona/administração & dosagem
Nordazepam/urina
Oxazepam/urina
Estudos Retrospectivos
Manejo de Espécimes
Temazepam/urina
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cytochrome P-450 CYP3A Inhibitors); 01K63SUP8D (Fluoxetine); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam); EC 1.14.13.67 (CYP3A4 protein, human); EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases); EC 1.14.14.1 (CYP2C19 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP2C19); EC 1.14.14.1 (Cytochrome P-450 CYP3A); N3PA6559FT (Esomeprazole); Q3JTX2Q7TU (Diazepam); UC6VBE7V1Z (Methadone)
[Em] Mês de entrada:1411
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140207
[St] Status:MEDLINE
[do] DOI:10.1093/jat/bku001


  10 / 469 MEDLINE  
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[PMID]:24314534
[Au] Autor:Wang R; Wang X; Liang C; Ni C; Xiong L; Rao Y; Zhang Y
[Ad] Endereço:Shanghai Institute of Forensic Science, Shanghai Key Laboratory of Crime Scene Evidence, Shanghai 200083, China.
[Ti] Título:Direct determination of diazepam and its glucuronide metabolites in human whole blood by µElution solid-phase extraction and liquid chromatography-tandem mass spectrometry.
[So] Source:Forensic Sci Int;233(1-3):304-11, 2013 Dec 10.
[Is] ISSN:1872-6283
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:A µElution solid-phase extraction (SPE) liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of diazepam, nordiazepam, oxazepam, oxazepam glucuronide, temazepam and temazepam glucuronide in human whole blood is presented. 200 µL of whole blood samples were loaded onto a Waters Oasis HLB 96-well µElution SPE plate using 75 µL of methanol as the elution solvent, and the eluents were injected into an Eclipse XDB C18 column. No hydrolysis, solvent transfer, evaporation or reconstitution was involved in the sample preparation procedures. Tandem mass spectrometric detection with Turbo Ion Spray was conducted via multiple reaction monitoring (MRM) under positive ionization mode. The method was validated and proved to be accurate (accuracy within 93-108%), precise (intra-day RSD<9.9% and inter-day RSD<7.2%) and sensitive with limits of detection (LOD) in the range of 0.05-0.25 ng/mL for all the compounds. Extraction recoveries were in the range of 31-80% for all the analytes. This method demonstrated to be reproducible and reliable. The applicability of the method was demonstrated by analysis of several forensic cases involving diazepam and its metabolites.
[Mh] Termos MeSH primário: Cromatografia Líquida
Diazepam/sangue
Hipnóticos e Sedativos/sangue
Extração em Fase Sólida/métodos
Espectrometria de Massas em Tandem
[Mh] Termos MeSH secundário: Toxicologia Forense/métodos
Seres Humanos
Limite de Detecção
Nordazepam/sangue
Oxazepam/análogos & derivados
Oxazepam/sangue
Reprodutibilidade dos Testes
Temazepam/análogos & derivados
Temazepam/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 26IK2C76NO (oxazepam glucuronide); 3703-53-5 (temazepam glucuronide); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1409
[Cu] Atualização por classe:161128
[Lr] Data última revisão:
161128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131210
[St] Status:MEDLINE



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