Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 41
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Pharmacogenet Genomics ; 23(3): 135-41, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23344581

RESUMO

BACKGROUND: Bupropion, an antidepressant and smoking cessation medication, is metabolized to hydroxybupropion (HB), an active metabolite, primarily by CYP2B6. OBJECTIVES: To compare plasma concentrations of bupropion and metabolites at steady state in healthy volunteers with and without CYP2B6 genetic variants. METHODS: In a genotype-guided study of 42 healthy individuals, we measured the plasma and urine concentrations of bupropion and its metabolites, HB, threohydrobupropion, and erythrohydrobupropion after 7 days of sustained-release bupropion dosing. RESULTS: CYP2B6*6 and *18 gene variants were associated with ~33% reduced concentrations of HB, with no effects on concentrations of bupropion or other metabolites. We could account for 50% of the variation in HB concentrations in a model including genotype and sex. CONCLUSION: As HB is active and its steady-state concentrations are more than 10 times higher than bupropion, CYP2B6 variants are likely to affect pharmacological activity. Because of the large individual variation within the genotype group, the use of therapeutic drug monitoring for dose optimization may be necessary.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Bupropiona/sangue , Bupropiona/urina , Inibidores da Captação de Dopamina/sangue , Inibidores da Captação de Dopamina/urina , Variação Genética , Oxirredutases N-Desmetilantes/genética , Sequência de Bases , Citocromo P-450 CYP2B6 , Primers do DNA , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase
2.
Anal Bioanal Chem ; 405(30): 9723-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23685960

RESUMO

The use of thin-film solid-phase microextraction (SPME) as the sampling preparation step before direct analysis in real time (DART) was evaluated for the determination of two prohibited doping substances, cocaine and methadone, in urine samples. Results showed that thin-film SPME improves the detectability of these compounds: signal-to-blank ratios of 5 (cocaine) and 13 (methadone) were obtained in the analysis of 0.5 ng/ml in human urine. Thin-film SPME also provides efficient sample cleanup, avoiding contamination of the ion source by salt residues from the urine samples. Extraction time was established in 10 min, thus providing relatively short analysis time and high throughput when combined with a 96-well shaker and coupled with DART technique.


Assuntos
Cocaína/urina , Inibidores da Captação de Dopamina/urina , Metadona/urina , Entorpecentes/urina , Microextração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Cocaína/isolamento & purificação , Inibidores da Captação de Dopamina/isolamento & purificação , Humanos , Metadona/isolamento & purificação , Entorpecentes/isolamento & purificação
3.
Am J Forensic Med Pathol ; 30(4): 391-3, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19901809

RESUMO

Parasailing is a recreational sport that is generally considered to be of little risk to the participants. Typically, the passenger launches from a motorboat with a specially designed winch that pulls him or her back to the boat at the end of the ride. The sport is not regulated at the federal, state, or county level. There have been few reports of injuries to parasailors. Additionally, there have been only 2 fatalities reported to the United States Coast Guard in a 10-year review. We report the details of these 2 deaths, those of a mother and daughter riding in a tandem parasail, which occurred on Fort Myers Beach in 2001, as well as an additional case of a parasailing fatality that occurred in southwest Florida in 1999. These cases illustrate the injuries seen in such fatalities and the hazards posed by adverse weather conditions and faulty equipment, as well as the impairment of passenger judgment by drugs and/or alcohol.


Assuntos
Traumatismo Múltiplo/patologia , Recreação , Vento , Ferimentos não Penetrantes/patologia , Adolescente , Adulto , Depressores do Sistema Nervoso Central/sangue , Depressores do Sistema Nervoso Central/urina , Cocaína/análogos & derivados , Cocaína/sangue , Cocaína/urina , Inibidores da Captação de Dopamina/sangue , Inibidores da Captação de Dopamina/urina , Falha de Equipamento , Etanol/sangue , Etanol/urina , Feminino , Florida , Patologia Legal , Humanos , Masculino , Equipamentos Esportivos
4.
Drug Metab Dispos ; 36(1): 24-35, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17908924

RESUMO

Brasofensine is an inhibitor of the synaptic dopamine transporter. These studies were conducted to characterize the pharmacokinetics, absolute bioavailability, disposition, and metabolism of brasofensine after i.v. and/or p.o. administrations of [(14)C]brasofensine in rats (1.5 mg/kg i.v., 4 mg/kg p.o.) and monkeys (4 mg i.v., 12 mg p.o.) and humans (50 mg p.o.). Brasofensine was rapidly absorbed after p.o. administration in rats and monkeys, with peak plasma concentrations occurring 0.5 to 1 h but 3 to 8 h for brasofensine in humans. Plasma terminal elimination half-lives were approximately 2 h in rats, approximately 4 h in monkeys, and approximately 24 h in humans. Total body clearance and steady-state volume of distribution values were 199 ml/min/kg and 24 l/kg, respectively, in the rat and 32 ml/min/kg and 46 l/kg, respectively, in the monkey. Absolute bioavailability was 7% in rats and 0.8% in monkeys. After a single p.o. dose, urinary excretion of radioactivity accounted for 20% of the administered dose in rats, 70% in monkeys, and 86% in humans, with the remainder excreted into the feces. Brasofensine had extensive first-pass metabolism following p.o. administration in humans, monkeys, and rats. It primarily underwent O- and N-demethylation and isomerization. Some of the desmethyl metabolites were further converted to glucuronides. These primary metabolites and glucuronides of demethyl brasofensine (M1 and M2) were major circulating metabolites in humans and were also observed in rat and monkey plasma.


Assuntos
Inibidores da Captação de Dopamina/farmacocinética , Compostos Heterocíclicos com 2 Anéis/farmacocinética , Oximas/farmacocinética , Administração Oral , Animais , Radioisótopos de Carbono , Inibidores da Captação de Dopamina/sangue , Inibidores da Captação de Dopamina/metabolismo , Inibidores da Captação de Dopamina/urina , Compostos Heterocíclicos com 2 Anéis/sangue , Compostos Heterocíclicos com 2 Anéis/metabolismo , Compostos Heterocíclicos com 2 Anéis/urina , Humanos , Injeções Intravenosas , Macaca fascicularis , Masculino , Taxa de Depuração Metabólica , Oximas/sangue , Oximas/metabolismo , Oximas/urina , Ratos , Ratos Long-Evans , Especificidade da Espécie , Distribuição Tecidual
5.
Talanta ; 175: 338-346, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28842000

RESUMO

We report a novel colorimetric biosensor based on non-aggregation Au@Ag core-shell nanoparticles to detect methamphetamine and cocaine. The biosensor consisted of a reporter probe (RP) that is a specific single-stranded DNA (ssDNA) sequence coated on Au@Ag nanoparticles, a capture probe (CP) conjugated with magnetic beads, and an illicit drug-binding DNA aptamer (Apt). Au@Ag nanoparticles were synthesized by seed growth and characterized by scanning electron microscope (SEM), high-resolution transmission electron microscopy (HR-TEM), and UV-vis spectra. Methamphetamine (METH) was used as an example to evaluate the feasibility of the biosensor and to optimize the detection conditions. We demonstrated that this sensing platform was able to detect as low as 0.1nM (14.9ngL-1) METH with a negligible interference from other common illicit drugs. Various concentrations of METH were spiked into urines, and the biosensor yielded recoveries more than 83.1%. In addition, the biosensor also showed a high sensitivity to detect cocaine. These results demonstrated that our colorimetric sensor holds promise to be implemented as a visual sensing platform to detect multiple illicit drugs in biological samples and environmental matrices.


Assuntos
Cocaína/urina , Colorimetria/métodos , Ouro/química , Nanopartículas Metálicas/química , Metanfetamina/urina , Prata/química , Detecção do Abuso de Substâncias/métodos , Técnicas Biossensoriais/métodos , Estimulantes do Sistema Nervoso Central/urina , Inibidores da Captação de Dopamina/urina , Humanos , Limite de Detecção , Nanopartículas Metálicas/ultraestrutura
6.
Drug Test Anal ; 9(1): 106-114, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26888521

RESUMO

Monitoring population drug use through wastewater-based epidemiology (WBE) is a useful method to quantitatively follow trends and estimate total drug consumption in communities. Concentrations of drug biomarkers might be low in wastewater due to dilution; and therefore analysis of pooled urine (PU) is useful to detect consumed drugs and identify targets of illicit drugs use. The aims of the study were (1) to screen PU and urinated soil (US) samples collected at festivals for illicit drug excretion products using hyphenated techniques; (2) to develop and validate a hydrophilic interaction liquid chromatography - mass spectrometry / mass spectrometry (HILIC-MS/MS) method of quantifying urinary targets of identified drugs in wastewater; and (3) to conduct a 24 h stability study, using PU and US to better reflect the chemical environment for targets in wastewater. Cocaine (COC) and ecstasy-like compounds were the most frequently detected illicit drugs; an analytical method was developed to quantify their excretion products. Hydroxymethoxymethamphetamine (HMMA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), HMMA sulfate (HMMA-S), benzoylecgonine (BE), and cocaethylene (CE) had 85-102% of initial concentration after 8 h of incubation, whereas COC and ecgonine methyl ester (EME) had 74 and 67% after 8 h, respectively. HMMA showed a net increase during 24 h of incubation (107% ± 27, n = 8), possibly due to the cleavage of HMMA conjugates, and biotransformation of MDMA. The results suggest HMMA as analytical target for MDMA consumption in WBE, due to its stability in wastewater and its excretion as the main phase I metabolite of MDMA. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
3,4-Metilenodioxianfetamina/análogos & derivados , Cocaína/urina , Poluentes Ambientais/análise , Drogas Ilícitas/urina , N-Metil-3,4-Metilenodioxianfetamina/urina , Detecção do Abuso de Substâncias/métodos , Águas Residuárias/análise , 3,4-Metilenodioxianfetamina/análise , 3,4-Metilenodioxianfetamina/urina , Inibidores da Captação Adrenérgica/análise , Inibidores da Captação Adrenérgica/urina , Cocaína/análise , Inibidores da Captação de Dopamina/análise , Inibidores da Captação de Dopamina/urina , Poluentes Ambientais/urina , Humanos , Drogas Ilícitas/análise , Limite de Detecção , N-Metil-3,4-Metilenodioxianfetamina/análise , Solo/química
7.
Leg Med (Tokyo) ; 8(3): 184-7, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16516527

RESUMO

Qualitative identification of cocaine and its metabolites in urine samples is generally carried out by an immunoassay technique followed by a gas chromatographic/mass spectrometric confirmation of presumptive positives. Nevertheless, other chromatographic techniques such as thin-layer chromatography or gas chromatography could also be used to screen several types of drugs of abuse especially for forensic and legal purposes. In the present work, the capability of high performance thin-layer chromatography (HPTLC) to detect cocaine in urine samples and discriminate it from interfering substances (local anaesthetic, caffeine and nicotine) was studied. Twenty urine samples of drug addicts were submitted to the HPTLC method. Unaltered cocaine present in the urine samples and cocaine obtained after methylation of benzoylecgonine (main cocaine metabolite) with diazomethane were detected in all tested samples. In conclusion, the proposed HPTLC method showed to be useful to detect cocaine in biological matrices.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cocaína/urina , Inibidores da Captação de Dopamina/urina , Detecção do Abuso de Substâncias/métodos , Anestésicos Locais/urina , Cafeína/urina , Estimulantes do Sistema Nervoso Central/urina , Cocaína/análogos & derivados , Medicina Legal , Estimulantes Ganglionares/urina , Humanos , Nicotina/urina
9.
Eur Neuropsychopharmacol ; 26(1): 37-44, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26655188

RESUMO

UNLABELLED: Recent animal studies demonstrate that compulsive cocaine seeking strongly reduces prelimbic frontal cortex activity, while optogenetic stimulation of this brain area significantly inhibits compulsive cocaine seeking, providing a strong rationale for applying brain stimulation to reduce cocaine consumption. Thus, we employed repetitive transcranial magnetic stimulation (rTMS), to test if dorsolateral prefrontal cortex (DLPFC) stimulation might prevent cocaine use in humans. Thirty-two cocaine-addicted patients were randomly assigned to either the experimental group (rTMS) on the left DLPFC, or to a control group (pharmacological agents) during a 29-day study (Stage 1). This was followed by a 63-day follow-up (Stage 2), during which all participants were offered rTMS treatment. Amongst the patients who completed Stage 1, 16 were in the rTMS group (100%) and 13 in the control group (81%). No significant adverse events were noted. During Stage 1, there were a significantly higher number of cocaine-free urine drug tests in the rTMS group compared to control (p=0.004). Craving for cocaine was also significantly lower in the rTMS group compared to the controls (p=0.038). Out of 13 patients who completed Stage 1 in the control group, 10 patients received rTMS treatment during Stage 2 and showed significant improvement with favorable outcomes becoming comparable to those of the rTMS group. The present preliminary findings support the safety of rTMS in cocaine-addicted patients, and suggest its potential therapeutic role for rTMS-driven PFC stimulation in reducing cocaine use, providing a strong rationale for developing larger placebo-controlled studies. Trial name: Repetitive transcranial magnetic stimulation (rTMS) in cocaine abusers, URL:〈http://www.isrctn.com/ISRCTN15823943?q=&filters=&sort=&offset=8&totalResults=13530&page=1&pageSize=10&searchType=basic-search〉, REGISTRATION NUMBER: ISRCTN15823943.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/terapia , Córtex Pré-Frontal , Estimulação Magnética Transcraniana/métodos , Adulto , Cocaína/administração & dosagem , Cocaína/urina , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Fissura , Depressão/fisiopatologia , Depressão/terapia , Inibidores da Captação de Dopamina/administração & dosagem , Inibidores da Captação de Dopamina/urina , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Projetos Piloto , Córtex Pré-Frontal/fisiopatologia , Estimulação Magnética Transcraniana/efeitos adversos , Resultado do Tratamento
10.
Clin Toxicol (Phila) ; 54(7): 568-75, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27412885

RESUMO

CONTEXT: An increasing number of new psychoactive substances (NPS) of different chemical classes have become available through marketing and sale over the Internet. This report from the Swedish STRIDA project presents the prevalence, laboratory results, and clinical features in a series of intoxications involving the stimulant NPS α-pyrrolidinovalerophenone (α-PVP), a potent dopamine re-uptake inhibitor, over a 4-year period. STUDY DESIGN: Observational case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals in Sweden from 2012 to 2015. PATIENTS AND METHODS: In the STRIDA project, blood and urine samples are collected from intoxicated patients with admitted or suspected intake of NPS or unknown drugs presenting to hospitals over the country. Analysis of NPS is performed by mass spectrometry multicomponent methods. Clinical data are collected when caregivers consult the Swedish Poisons Information Centre (PIC), and retrieved from medical records. The severity of poisoning is graded retrospectively using the Poisoning Severity Score (PSS). The inclusion criteria for this study included absence of other stimulants than α-PVP. RESULTS: During the 4-year study period, 23 intoxications were originally coded as "α-PVP related" out of a total 3743 NPS-related inquiries (0.6%) at the PIC. The present study covered 42 analytically confirmed cases in which α-PVP was the only stimulant detected. The age range of patients was 20-58 (median 32) years, of which 79% were males. The α-PVP concentration in serum was 4.0-606 (median 64; n = 42) ng/mL and 2.0-41,294 (median 1782; n = 25) ng/mL in urine. There was no statistically significant association between the serum α-PVP concentration and urinary α-PVP/creatinine ratio in 25 cases, where both sets of data were available. In 14/42 (33%) cases, α-PVP was the only psychoactive substance identified. In the remaining cases, additional substances comprised opioids, benzodiazepines, and ethanol. The main clinical manifestations were tachycardia (80%), agitation (70%), hypertension (33%), hallucinations (20%), and delirium (18%). Classification of poisoning severity yielded 25 (60%) moderate (PSS 2), 7 (17%) severe (PSS 3), and 2 fatal cases (PSS 4). CONCLUSIONS: In analytically confirmed α-PVP intoxication cases involving no other stimulant drugs, the urine and serum concentrations showed high variability. The clinical features were consistent with a severe sympathomimetic toxidrome. The results further demonstrated that α-PVP prevailed as a drug of abuse after being classified as a narcotic substance, and despite a high incidence of severe poisonings and fatalities. However, the low prevalence of α-PVP cases registered at the PIC suggested that many were unaware of the actual substance they had taken.


Assuntos
Estimulantes do Sistema Nervoso Central/intoxicação , Drogas Ilícitas/intoxicação , Pirrolidinas/intoxicação , Adulto , Analgésicos Opioides/sangue , Analgésicos Opioides/intoxicação , Analgésicos Opioides/urina , Benzodiazepinas/sangue , Benzodiazepinas/intoxicação , Benzodiazepinas/urina , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/urina , Creatinina/urina , Delírio/induzido quimicamente , Delírio/diagnóstico , Inibidores da Captação de Dopamina/sangue , Inibidores da Captação de Dopamina/intoxicação , Inibidores da Captação de Dopamina/urina , Etanol/sangue , Etanol/intoxicação , Etanol/urina , Feminino , Alucinações/induzido quimicamente , Alucinações/diagnóstico , Hospitalização , Humanos , Hipertensão/induzido quimicamente , Hipertensão/diagnóstico , Drogas Ilícitas/sangue , Drogas Ilícitas/urina , Masculino , Pessoa de Meia-Idade , Prevalência , Agitação Psicomotora/diagnóstico , Agitação Psicomotora/etiologia , Pirrolidinas/sangue , Pirrolidinas/urina , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/etiologia , Suécia , Taquicardia/induzido quimicamente , Taquicardia/diagnóstico , Adulto Jovem
11.
Drug Alcohol Depend ; 79(2): 257-60, 2005 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-16002035

RESUMO

The purpose of this double-blind, outpatient study was to evaluate the reinforcing and subjective effects of the uncompetitive N-methyl-d-aspartate (NMDA) antagonist memantine in cocaine-dependent humans. Eight participants (two females, six males) completed this study which consisted of three blocks of seven sessions; each block tested a different dose of memantine. During the first two sessions of each block, participants "sampled" the memantine capsule (10, 20, or 30 mg) and the placebo capsule that were available for the next five sessions. During the five subsequent sessions, participants had an opportunity to self-administer either the active or placebo capsule. Memantine was not reinforcing and subjective-effects ratings were not altered as a function of dose. Results suggest that these doses of memantine do not have abuse liability in cocaine-dependent individuals.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Dopaminérgicos/uso terapêutico , Memantina/uso terapêutico , N-Metilaspartato/antagonistas & inibidores , Reforço Psicológico , Adulto , Assistência Ambulatorial , Cocaína/urina , Transtornos Relacionados ao Uso de Cocaína/urina , Inibidores da Captação de Dopamina/urina , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino
12.
J Forensic Sci ; 50(6): 1481-5, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16382849

RESUMO

Toxicological evaluation of postmortem urine collected from a 41-year-old deceased white male detected anhydroecgonine ethyl ester (ethylecgonidine, AEEE), a transesterification product of smoked cocaine co-abused with ethanol. A solid phase extraction (SPE) method was used to extract cocaine, AEEE, and related metabolites from urine. SPE on a 1 mL urine sample from the decedent followed by GC-MS detected AEEE. Other metabolites identified by GC-MS included cocaine, cocaethylene, and anhydroecgonine methyl ester (AEME). To determine whether some or all of the AEEE was artifactually produced in the heated GC injector port, an alternative LC-MS method was developed. LC/MS following SPE found at least 50 ng/mL of AEEE in the extract. The mass fragmentation (MS/MS and MS3) of AEEE detected in the urine was compared to spectra of authentic, synthesized compound. AEEE is a potential additional forensic marker for the co-abuse of smoked cocaine and ethanol.


Assuntos
Cocaína/análogos & derivados , Inibidores da Captação de Dopamina/intoxicação , Inibidores da Captação de Dopamina/urina , Adulto , Alcoolismo/sangue , Depressores do Sistema Nervoso Central/sangue , Cromatografia Líquida de Alta Pressão , Cocaína/intoxicação , Cocaína/urina , Transtornos Relacionados ao Uso de Cocaína/urina , Overdose de Drogas , Etanol/sangue , Medicina Legal , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Espectrometria de Massas
13.
Clin Toxicol (Phila) ; 53(9): 865-73, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26462932

RESUMO

CONTEXT: In the recent years, there have been an increasing number of new psychoactive substances (NPS) available through marketing and sale on the Internet. The stimulant 3,4-methylenedioxypyrovalerone (MDPV) is a potent dopamine reuptake inhibitor, which can cause serious intoxications requiring intensive care and even fatality. This report from the STRIDA project presents the prevalence, laboratory results, and clinical features in a series of intoxications involving MDPV over a 5-year period. STUDY DESIGN: Observational case series of consecutive patients with admitted or suspected intake of NPS presented at hospitals in Sweden from 2010 to 2014. PATIENTS AND METHODS: Blood and/or urine samples were collected from intoxicated patients with admitted or suspected intake of NPS presenting at hospitals over the country. Analysis of NPS was performed by a liquid chromatography-tandem mass spectrometry multicomponent method. Clinical data were collected when caregivers consulted the Swedish Poisons Information Centre and also retrieved from medical records. The severity of poisoning was graded retrospectively using the poisoning severity score. RESULTS: During the 5-year study period, the number of MDPV-related inquiries to the Poisons Information Centre was 662 out of a total ∼4500 suspected NPS-related inquiries (∼15%), and 201 analytically confirmed MDPV intoxications were enrolled in the study. The study period covered the period when the use of MDPV in Sweden was at its peak and also the decline to an almost zero level. The age range of patients was 18-68 (mean 36, median 35) years, and 71% were males. The MDPV concentrations in serum ranged between 1.0 ng/mL and 1509 ng/mL (mean 63.6, median 20) and between 1.0 ng/mL and 81 000 ng/mL (mean 3880, median 1160) in urine. The urinary values were also creatinine corrected for variation in urine dilution, and the MDPV/creatinine ratio ranged between 0.10 ng/mmol and 2480 ng/mmol (mean 247, median 92.6). There was a statistically significant association between the serum MDPV concentration and the urinary MDPV/creatinine ratio, for 118 cases where both data were available (r = 0.764; p < 0.0001, Spearman's rank correlation). In 30 (15%) cases, MDPV was the single psychoactive substance identified in the serum or urine specimens. In the other 171 cases, other psychoactive substances were detected together with MDPV. The additional substances (n = 61) comprised of both conventional drugs of abuse, other NPS (n = 39), pharmaceuticals, and ethanol. The cathinone-derivative alpha-pyrrolidinovalerophenone (α-PVP) was the most frequent other NPS, and was detected in 58 (29%) cases, followed by methylone in 14 (7%) cases. The main clinical manifestations reported in patients testing positive for MDPV included agitation, tachycardia (≥100/min), and hypertension (systolic blood pressure ≥140 mmHg), which were observed in 130 (67%), 106 (56%), and 65 (34%) cases, respectively. Other symptoms included hallucinations (n = 31, 16%), delirium (n = 29, 15%), hyperthermia (>39°C/102.4°F; n = 18, 10%), and rhabdomyolysis (n = 16, 8%). In MDPV intoxications with serum levels >100 ng/mL, the cases were graded as more severe and hyperthermia was less common. CONCLUSIONS: In a large number of analytically confirmed MDPV intoxications from mostly polydrug users, the urine and serum MDPV concentrations showed a high variability. The clinical features were consistent with a severe sympathomimetic toxidrome. The results also demonstrated that MDPV prevailed as a drug of abuse for a long time, after its classification as a narcotic substance and despite a high incidence of severe poisonings.


Assuntos
Benzodioxóis/intoxicação , Inibidores da Captação de Dopamina/intoxicação , Psicotrópicos/intoxicação , Pirrolidinas/intoxicação , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Idoso , Benzodioxóis/sangue , Benzodioxóis/urina , Biomarcadores/sangue , Biomarcadores/urina , Cromatografia Líquida , Inibidores da Captação de Dopamina/sangue , Inibidores da Captação de Dopamina/urina , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Centros de Controle de Intoxicações , Valor Preditivo dos Testes , Prevalência , Psicotrópicos/sangue , Psicotrópicos/urina , Pirrolidinas/sangue , Pirrolidinas/urina , Estudos Retrospectivos , Índice de Gravidade de Doença , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Suécia/epidemiologia , Espectrometria de Massas em Tandem , Fatores de Tempo , Adulto Jovem , Catinona Sintética
14.
Am J Clin Pathol ; 106(6): 701-4, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8980344

RESUMO

Cocaethylene (CE) and cocaine (COC) concentrations were reviewed for 41 patients studied by this laboratory and found to have measurable CE in plasma. In 17 instances, urine concentrations of CE and COC were also measured. In 15 cases other drugs in addition to COC and ethanol (ETOH) were detected. Thirty-three cases involved trauma. For the entire series, ages ranged from 19 to 48 years (mean 31 years) with men accounting for 36 cases. Mean concentrations were as follows: plasma CE, 353 nmol/L (range 16.1-1,959); plasma COC, 386 nmol/L (range no measurable amount-1,455); and whole-blood ETOH, 36.5 mmol/L (range no measurable amount-110.9). The ratio CE:COC in plasma ranged 0.1 to 4.7 (mean 1.3). Concentrations of ETOH in whole blood showed significant negative correlation with plasma COC (r = -0.425, P < .01). In addition, plasma CE concentrations showed significant correlation with plasma COC (r = 0.422, P < .01). When available, urine concentrations of CE and COC showed significant correlation with their concentrations in plasma (r = 0.821, P < .01; and r = 0.569, P < .05, respectively). As in plasma, urine concentrations of CE showed significant correlation with urine COC (r = 0.831, P < .01).


Assuntos
Cocaína/análogos & derivados , Cocaína/sangue , Inibidores da Captação de Dopamina/sangue , Adulto , Depressores do Sistema Nervoso Central/sangue , Cromatografia Líquida de Alta Pressão , Cocaína/urina , Inibidores da Captação de Dopamina/urina , Etanol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Drug Alcohol Depend ; 72(2): 169-82, 2003 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-14636972

RESUMO

BACKGROUND: Concurrent use of cocaine and alcohol results in formation of a cocaine homolog and metabolite-cocaethylene. METHODS: To characterize cocaethylene pharmacology, ten paid volunteer subjects were given deuterium-labeled (d(5)) cocaine (0.3, 0.6, and 1.2 mg/kg and cocaine placebo) by a 15-min constant rate intravenous injection 1 h after a single oral dose of ethanol (1 g/kg) or ethanol and cocaine placebo using a double-blind, crossover design. Six of the same volunteers subsequently received a 1.2 mg/kg dose of cocaine alone. A small (7.5 mg) nonpharmacologically active dose of deuterium-labeled cocaethylene-d(3) was concurrently administered with the cocaine to enable calculation of absolute cocaethylene formation and clearance. Plasma and urine cocaine, cocaethylene, and benzoylecgonine concentrations, physiologic and subjective effects were measured. RESULTS: When co-administered with ethanol, 17+/-6% (mean+/-S.D.) of the cocaine was converted to cocaethylene. Cocaethylene peak plasma concentrations and AUC increased proportionally to the cocaine dose. Ethanol ingestion prior to cocaine administration decreased urine benzoylecgonine levels by 48% and increased urinary cocaethylene and ecgonine ethyl ester levels. Subjects liked and experienced more total intoxication after the combination of cocaine and ethanol than after either drug alone. CONCLUSIONS: In the presence of ethanol, the altered biotransformation of cocaine resulted in 17% of an intravenous cocaine dose being converted to cocaethylene and relatively lower urinary concentrations of benzoylecgonine.


Assuntos
Cocaína/análogos & derivados , Cocaína/farmacocinética , Inibidores da Captação de Dopamina/farmacologia , Etanol/farmacocinética , Adulto , Pressão Sanguínea/efeitos dos fármacos , Cromatografia , Cocaína/administração & dosagem , Cocaína/sangue , Cocaína/urina , Estudos Cross-Over , Inibidores da Captação de Dopamina/sangue , Inibidores da Captação de Dopamina/urina , Relação Dose-Resposta a Droga , Método Duplo-Cego , Interações Medicamentosas , Etanol/administração & dosagem , Etanol/sangue , Etanol/urina , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Taxa de Depuração Metabólica
16.
J Pharm Biomed Anal ; 13(3): 305-12, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7619891

RESUMO

Cocaethylene is an active metabolite produced when cocaine is consumed jointly with ethanol. The development of analytical techniques for determining cocaethylene and other cocaine metabolites is highly relevant for pharmacokinetic and toxicology studies of the cocaine and alcohol interaction in humans. The gas chromatography/mass spectrometry (GC/MS) method here reported is based on a single solid-phase extraction together with deuterated internal standards previously added to urine, followed by derivatization with pentafluoropropionic anhydride (hydroxyl and amine functions) and 1,1,1,3,3,3 hexafluor-2-propanol (carboxylic acid function) and injection into a capillary GC system coupled to a mass spectrometric detector in the selected ion monitoring acquisition mode. A sensitivity of 1-2 ng ml-1 for the quantitative analysis of cocaine and its main metabolites (ecgonine methyl ester, benzoylecgonine, cocaethylene and norcocaine) was achieved. In addition, some other minor metabolites were easily extracted and detected.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Cocaína/urina , Transtornos Relacionados ao Uso de Substâncias/urina , Adulto , Biotransformação , Cocaína/análogos & derivados , Cocaína/farmacocinética , Inibidores da Captação de Dopamina/urina , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Indicadores e Reagentes , Masculino , Soluções
17.
Ann Clin Lab Sci ; 30(1): 85-91, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10678589

RESUMO

Testing for drugs of abuse in urine is commonplace in emergency departments and neonatal units. However, the clinical sensitivity of immunochemical screening methods is limited by the threshold concentrations used to distinguish between positive and negative specimens. Immunochemical screening methods for cocaine metabolite (benzoylecgonine), cannabinoids, and opiates in urine were recalibrated to detect drugs at lower threshold concentrations. The precision and linearity of the signals at the modified thresholds were verified by diluting drug-positive urine specimens to concentrations below the conventional cutoff concentration and measuring the rate signals in triplicate. To assess the clinical performance of the modified methods, specimens that tested negative using the unmodified assays were re-screened at the lower threshold, and specimens that re-screened positive were submitted for gas chromatographic/mass spectrometric (GC/MS) confirmation. Reproducibility of sub-threshold measurements was comparable to the unmodified assays, and rate separations between successive dilutions were sufficient to give semi-quantitative results. Using the lower thresholds, drugs were detected in 4-5% of the subjects that had screened negative at the conventional threshold concentration. GC/MS analysis confirmed the presence of cannabinoids and cocaine metabolite in 74% and 84%, respectively, of urine specimens that re-screened positive. Morphine, codeine, hydromorphone, or hydrocodone was detected by GC/MS analysis in 31% of opiate-positive re-screens.


Assuntos
Canabinoides/análise , Cocaína/análise , Inibidores da Captação de Dopamina/análise , Entorpecentes/análise , Detecção do Abuso de Substâncias/métodos , Adulto , Canabinoides/urina , Cocaína/urina , Inibidores da Captação de Dopamina/urina , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Drogas Ilícitas/análise , Drogas Ilícitas/urina , Imunoensaio/métodos , Imunoensaio/normas , Recém-Nascido , Entorpecentes/urina , Síndrome de Abstinência Neonatal/diagnóstico , Síndrome de Abstinência Neonatal/urina , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Forensic Sci Int ; 143(2-3): 187-90, 2004 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-15240042

RESUMO

National surveys of the UK drug situation in 2000 found that cocaine was the most frequently seized Class A drug, with 25-40 tonnes of cocaine being smuggled into the UK each year. In the light of these findings, an audit of the analytical monitoring for cocaine abuse has been performed covering the period from 1996 to 2002. It was found that there has been a consistent upward trend in the percentage of requests found to be positive for cocaine over this 7-year study period, rising from 9.7% in 1996 to 22% in 2002. This data would suggest that the use of cocaine has increased dramatically over the past few years, indicating that the arrival of the "cocaine epidemic" has now started to become a reality in the UK.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Cocaína/urina , Transtornos Relacionados ao Uso de Cocaína/urina , Inibidores da Captação de Dopamina/urina , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino Unido/epidemiologia
19.
Forensic Sci Int ; 133(3): 256-9, 2003 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-12787662

RESUMO

We report a case of intoxication resulting from the ingestion of a liquid, sold in the illicit market as "liquid ecstasy," which was found to contain 1,4-butanediol, a metabolic precursor of gamma-hydroxybutiric acid (GHB). Identification of the substance in the liquid was performed by gas chromatography-mass spectrometry (GC-MS). The toxicological analysis of blood, urine and gastric content of the victim was performed by immunoassay and gas chromatography with nitrogen-phosphorus detection as screening techniques and by means of GC-MS for confirmation and quantitation of 1,4-butanediol and GHB. The following drug concentrations were found: 82 microg/ml (blood), 401 microg/ml (urine) and 7.4 microg/ml (gastric content) for 1,4-butanediol and 103 microg/ml (blood), 430.0 microg/ml (urine) for GHB. In addition to these, other drugs detected and their blood concentration found in this case were methylenedioxymethylamphetamine (MDMA) 0.23 microg/ml and its metabolite methylenedioxyphenylamphetamine (MDA) 0.10 microg/ml. In the urine, a concentration of 0.10 microg/ml of benzoylecgonine was also found.


Assuntos
Butileno Glicóis/intoxicação , Cocaína/análogos & derivados , Drogas Ilícitas/intoxicação , Butileno Glicóis/sangue , Butileno Glicóis/urina , Cocaína/urina , Inibidores da Captação de Dopamina/urina , Cromatografia Gasosa-Espectrometria de Massas , Conteúdo Gastrointestinal/química , Alucinógenos/sangue , Humanos , Drogas Ilícitas/sangue , Drogas Ilícitas/urina , Masculino , N-Metil-3,4-Metilenodioxianfetamina/sangue
20.
J Anal Toxicol ; 19(4): 247-50, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8531471

RESUMO

Cocaethylene (ethylcocaine) (CE) was incorporated into this laboratory's urine toxicological screening protocol more than 1 year ago. During a 1-year period, 451 urine specimens tested positive for benzoylecgonine (BE) and/or cocaine (COC) and/or CE using a combination of thin-layer chromatography with enzyme immunoassay confirmation. CE was detected in 57 urine specimens. Blood ethanol (EtOH) analysis was available for 37 of these cases, and the mean concentration (1320 mg/L) was significantly higher than that found in 117 blood EtOH assays performed for the CE-negative patients (630 mg/L) (p < .01). In two instances, CE was noted in urine in the absence of EtOH in the corresponding blood. Without exception, CE, when present in urine, was always detected with both BE and COC. Most of the time, no other drugs were found. In one instance, CE was present in the urine of a neonate but was not detected in that of its mother. Demographic and analytical findings are presented for both CE-positive and CE-negative cases.


Assuntos
Cocaína/análogos & derivados , Inibidores da Captação de Dopamina/urina , Adolescente , Adulto , California , Cromatografia em Camada Fina , Cocaína/urina , Estudos de Coortes , Feminino , Humanos , Técnicas Imunoenzimáticas , Recém-Nascido , Pacientes Internados , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA