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[PMID]:28450464
[Au] Autor:Luo X; Gong X; Zhao P; Zou X; Chen W; Ling L
[Ad] Endereço:Faculty of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen Center for Migrant Health Policy, Sun Yat-Sen University, Guangzhou, China.
[Ti] Título:Positive percentages of urine morphine tests among methadone maintenance treatment clients with HIV/AIDS: a 12-month follow-up study in Guangdong Province, China.
[So] Source:BMJ Open;7(4):e014237, 2017 04 27.
[Is] ISSN:2044-6055
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: We aimed to assess the positive percentages of urine morphine tests and correlates among methadone maintenance treatment (MMT) clients with HIV/AIDS in Guangdong, China. SETTING: Fourteen MMT clinics located in nine cities of Guangdong were chosen as study sites. PARTICIPANTS: In this study, we reviewed 293 clients with opioid dependence, who were HIV seropositive, 18 years or older, provided informed consent and had at least 10 records of urine morphine tests during the study period. PRIMARY AND SECONDARY OUTCOME MEASURES: The positive percentages of urine morphine tests were calculated and underlying predictors were estimated. RESULTS: The highest positive percentage (95.9%) was observed in the first month. After excluding the highest percentage in the first month, the average positive percentage was 40.9% for month 2 to month 12. Positive percentages of urine morphine tests that were <20%, 20-60% and >80% were 25.4%, 36.1% and 38.5% respectively. Lower percentages of continued heroin use were associated with being young (OR =0.31, 95% CI 0.12 to 0.78; OR =0.44, 95% CI 0.20 to 1.00), and financial sources depending on family or friends (OR=0.55, 95% CI 0.32 to 0.93). Higher percentages of continued heroin use were associated with being unemployed (OR=1.99, 95% CI 1.13 to 3.49) and poor MMT attendance (OR =3.60, 95% CI 1.55 to 8.33; OR =2.80, 95% CI 1.48 to 5.33). CONCLUSIONS: High positive percentages of urine morphine tests remain prevalent among MMT clients with HIV/AIDS in Guangdong. The present findings have implications for taking effective measures to facilitate attendance in order to decrease heroin use and ultimately improve the effectiveness among these sub-group MMT clients.
[Mh] Termos MeSH primário: Síndrome de Imunodeficiência Adquirida/tratamento farmacológico
Metadona/uso terapêutico
Derivados da Morfina/urina
Transtornos Relacionados ao Uso de Opioides/diagnóstico
[Mh] Termos MeSH secundário: Adulto
China/epidemiologia
Feminino
Seguimentos
Seres Humanos
Masculino
Transtornos Relacionados ao Uso de Opioides/epidemiologia
Prevalência
Assunção de Riscos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Morphine Derivatives); UC6VBE7V1Z (Methadone)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1136/bmjopen-2016-014237


  2 / 1804 MEDLINE  
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[PMID]:29191644
[Au] Autor:Yadlapalli JSK; Dogra N; Walbaum AW; Prather PL; Crooks PA; Dobretsov M
[Ad] Endereço:Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
[Ti] Título:Preclinical assessment of utility of M6S for multimodal acute and chronic pain treatment in diabetic neuropathy.
[So] Source:Life Sci;192:151-159, 2018 Jan 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Previous reports from our laboratory have established that morphine-6-O-sulfate (M6S) is a mixed µ/δ opioid receptor (OR) agonist and a potential improved alternative to morphine for treatment of chronic multimodal pain in non-diabetic rats. This study extends the antinociceptive effects of M6S and morphine in STZ-induced diabetic rats. MATERIALS AND METHODS: Effects of morphine and M6S were studied across a range of pain modalities, using hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold (PPT) tests. KEY FINDINGS: Acutely, M6S was 3- to 5-fold more potent and 2- to 3-fold more efficacious than morphine in HPT and PST tests. No differences in analgesic drug potency/efficacy were detected in the PPT test. After 7-9days of chronic treatment, tolerance developed to the antinociceptive effects of morphine, but not to M6S, in all three pain tests. Furthermore, morphine-tolerant rats were not cross-tolerant to M6S. The selective δ-OR antagonist, naltrindole, blocked M6S-induced antinociception by 62±3% in the HPT test, 93±5% in the PST test, and 30±17% in the PPT test when examined acutely. SIGNIFICANCE: These studies provide additional confirmation for the mixed µ/δ activity of M6S and demonstrate potential improved clinical utility for dual µ/δ agonists relative to morphine in treatment of diabetic neuropathy across multiple pain domains.
[Mh] Termos MeSH primário: Analgésicos Opioides/uso terapêutico
Dor Crônica/tratamento farmacológico
Nefropatias Diabéticas/tratamento farmacológico
Derivados da Morfina/uso terapêutico
Dor/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Dor Crônica/etiologia
Diabetes Mellitus Experimental/complicações
Nefropatias Diabéticas/complicações
Masculino
Morfina/uso terapêutico
Dor/etiologia
Manejo da Dor
Medição da Dor/efeitos dos fármacos
Limiar da Dor/efeitos dos fármacos
Ratos
Ratos Sprague-Dawley
Receptores Opioides delta/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Morphine Derivatives); 0 (Receptors, Opioid, delta); 0 (morphine-6-O-sulfate); 76I7G6D29C (Morphine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE


  3 / 1804 MEDLINE  
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[PMID]:28651217
[Au] Autor:McCall AK; Palmitessa R; Blumensaat F; Morgenroth E; Ort C
[Ad] Endereço:Eawag, Swiss Federal Institute of Aquatic Science and Technology, CH 8600, Dübendorf, Switzerland.
[Ti] Título:Modeling in-sewer transformations at catchment scale - implications on drug consumption estimates in wastewater-based epidemiology.
[So] Source:Water Res;122:655-668, 2017 Oct 01.
[Is] ISSN:1879-2448
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To which extent illicit drugs are transformed during in-sewer transport, depends on a number of factors: i) substance-specific transformation rates, ii) environmental conditions, iii) point of discharge (location of drug user) and iv) sewer network properties, primarily hydraulic residence time (HRT) and the ratio of biofilm contact area to wastewater volume (A/V ). Assessing associated uncertainties typically requires numerous simulations. Therefore, we propose a new two-step modeling framework: 1) Quantify hydrodynamic conditions. This computationally demanding step was performed once in SWMM to derive HRT and A/V for each potential point of discharge (node) in three catchments of different size. 2) Estimate biomarker loss. In this step, Monte Carlo simulations were performed for defined scenarios. Depending on assumptions about drug user distribution and prevalence, a number of nodes was sampled. For each node an empirical first-order transformation model was applied with flow-path-corresponding HRT and A/V from step 1. Biotic and abiotic transformation rates were sampled from distributions combining variability of different biofilms. In our modeling study, median losses were >30% for amphetamine, 6-monoacetylmorphine and 6-acetylcodeine in all three catchments with high uncertainty (5%-100% loss), which would imply a systematic underestimation of consumption when neglecting in-sewer processes. Median losses for 21 other investigated biomarkers were <10% with different uncertainty ranges - "no substantial transformation" was confirmed for nine substances in a real sewer segment with a 2-h residence time. Transferability of these results must be tested for other catchments. To further reduce uncertainty, mainly additional knowledge on transformation rates, particularly in biofilm, and their distribution across a sewer network is needed to update model input objectively. Our approach allows efficient testing and, furthermore, can be expanded for many other human biomarkers. Accounting for biomarker stability during in-sewer transport will avoid biased estimates and further improve wastewater-based epidemiology.
[Mh] Termos MeSH primário: Esgotos/química
Águas Residuais
Poluentes Químicos da Água/química
[Mh] Termos MeSH secundário: Anfetamina/química
Codeína/análogos & derivados
Codeína/química
Derivados da Morfina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Morphine Derivatives); 0 (Sewage); 0 (Waste Water); 0 (Water Pollutants, Chemical); 6703-27-1 (acetylcodeine); CK833KGX7E (Amphetamine); M5E47P1ZCH (6-O-monoacetylmorphine); Q830PW7520 (Codeine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE


  4 / 1804 MEDLINE  
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[PMID]:28562278
[Au] Autor:Lind JN; Interrante JD; Ailes EC; Gilboa SM; Khan S; Frey MT; Dawson AL; Honein MA; Dowling NF; Razzaghi H; Creanga AA; Broussard CS
[Ad] Endereço:Division of Congenital and Developmental Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia; jlind@cdc.gov.
[Ti] Título:Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review.
[So] Source:Pediatrics;139(6), 2017 Jun.
[Is] ISSN:1098-4275
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CONTEXT: Opioid use and abuse have increased dramatically in recent years, particularly among women. OBJECTIVES: We conducted a systematic review to evaluate the association between prenatal opioid use and congenital malformations. DATA SOURCES: We searched Medline and Embase for studies published from 1946 to 2016 and reviewed reference lists to identify additional relevant studies. STUDY SELECTION: We included studies that were full-text journal articles and reported the results of original epidemiologic research on prenatal opioid exposure and congenital malformations. We assessed study eligibility in multiple phases using a standardized, duplicate review process. DATA EXTRACTION: Data on study characteristics, opioid exposure, timing of exposure during pregnancy, congenital malformations (collectively or as individual subtypes), length of follow-up, and main findings were extracted from eligible studies. RESULTS: Of the 68 studies that met our inclusion criteria, 46 had an unexposed comparison group; of those, 30 performed statistical tests to measure associations between maternal opioid use during pregnancy and congenital malformations. Seventeen of these (10 of 12 case-control and 7 of 18 cohort studies) documented statistically significant positive associations. Among the case-control studies, associations with oral clefts and ventricular septal defects/atrial septal defects were the most frequently reported specific malformations. Among the cohort studies, clubfoot was the most frequently reported specific malformation. LIMITATIONS: Variabilities in study design, poor study quality, and weaknesses with outcome and exposure measurement. CONCLUSIONS: Uncertainty remains regarding the teratogenicity of opioids; a careful assessment of risks and benefits is warranted when considering opioid treatment for women of reproductive age.
[Mh] Termos MeSH primário: Anormalidades Induzidas por Medicamentos
Analgésicos Opioides/efeitos adversos
Derivados da Morfina/efeitos adversos
Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
Complicações na Gravidez/tratamento farmacológico
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Metadona/efeitos adversos
Gravidez
Projetos de Pesquisa
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Morphine Derivatives); UC6VBE7V1Z (Methadone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170601
[St] Status:MEDLINE


  5 / 1804 MEDLINE  
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[PMID]:28489639
[Au] Autor:Yadlapalli JSK; Dogra N; Walbaum AW; Wessinger WD; Prather PL; Crooks PA; Dobretsov M
[Ad] Endereço:From the *Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and Departments of †Anesthesiology and ‡Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
[Ti] Título:Evaluation of Analgesia, Tolerance, and the Mechanism of Action of Morphine-6-O-Sulfate Across Multiple Pain Modalities in Sprague-Dawley Rats.
[So] Source:Anesth Analg;125(3):1021-1031, 2017 Sep.
[Is] ISSN:1526-7598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Morphine-6-O-sulfate (M6S) is a mixed µ/δ-opioid receptor (OR) agonist and potential alternative to morphine for treatment of chronic multimodal pain. METHODS: To provide more support for this hypothesis, the antinociceptive effects of M6S and morphine were compared in tests that access a range of pain modalities, including hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold tests. RESULTS: Acutely, M6S was 2- to 3-fold more potent than morphine in HPT and PST tests, specifically, derived from best-fit analysis of dose-response relationships of morphine/M6S half-effective dose (ED50) ratios (lower, upper 95% confidence interval [CI]) were 2.8 (2.0-5.8) in HPT and 2.2 (2.1, 2.4) in PST tests. No differences in analgesic drug potencies were detected in the PPT test (morphine/M6S ED50 ratio 1.2 (95% CI, 0.8-1.4). After 7 to 9 days of chronic treatment, tolerance developed to the antinociceptive effects of morphine, but not to M6S, in all 3 pain tests. Morphine-tolerant rats were not crosstolerant to M6S. The antinociceptive effects of M6S were not sensitive to κ-OR antagonists. However, the δ-OR antagonist, naltrindole, blocked M6S-induced antinociception by 55% ± 4% (95% CI, 39-75) in the HPT test, 94% ± 4% (95% CI, 84-105) in the PST test, and 5% ± 17% (95% CI, -47 to 59) or 51% ± 14% (95% CI, 14-84; 6 rats per each group) in the paw pressure threshold test when examined acutely or after 7 days of chronic treatment, respectively. CONCLUSIONS: Activity via δ-ORs thus appears to be an important determinant of M6S action. M6S also exhibited favorable antinociceptive and tolerance profiles compared with morphine in 3 different antinociceptive assays, indicating that M6S may serve as a useful alternative for rotation in morphine-tolerant subjects.
[Mh] Termos MeSH primário: Analgesia/métodos
Tolerância a Medicamentos
Derivados da Morfina/uso terapêutico
Manejo da Dor/métodos
Dor/tratamento farmacológico
[Mh] Termos MeSH secundário: Analgésicos Opioides/farmacologia
Analgésicos Opioides/uso terapêutico
Animais
Relação Dose-Resposta a Droga
Avaliação Pré-Clínica de Medicamentos/métodos
Masculino
Derivados da Morfina/farmacologia
Dor/patologia
Medição da Dor/efeitos dos fármacos
Medição da Dor/métodos
Ratos
Ratos Sprague-Dawley
Receptores Opioides delta/agonistas
Receptores Opioides mu/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Morphine Derivatives); 0 (Receptors, Opioid, delta); 0 (Receptors, Opioid, mu); 0 (morphine-6-O-sulfate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE
[do] DOI:10.1213/ANE.0000000000002006


  6 / 1804 MEDLINE  
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[PMID]:28335030
[Au] Autor:Høiseth G; Gottås A; Berg T; Arnestad M; Halvorsen PS; Bachs LC
[Ad] Endereço:Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway.
[Ti] Título:Urinary Kinetics of Heroin Metabolites in Pigs Shortly After Intake.
[So] Source:J Anal Toxicol;41(5):451-454, 2017 Jun 01.
[Is] ISSN:1945-2403
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In previous experimental studies on heroin metabolites excretion in urine, the first sample was often collected a few hours after intake. In forensic cases, it is sometimes questioned if a positive urine result is expected e.g., 30 min after intake. The aim of this study was to investigate urinary excretion of heroin metabolites (morphine, 6-monoacetylmorphine (6-MAM) and morphine-3-glucuronide (M3G)) every 30 min until 330 min after injection of a 20 mg heroin dose in six pigs. Samples were analyzed using a previously published, fully validated liquid chromatography-tandem mass spectrometry method. All metabolites were detected after 30 min in all pigs. The time to maximum concentration (Tmax) median (range) for 6-MAM and morphine was 30 min (first sample) (30-120), and 90 min (30-330) for M3G. In four of the six pigs, the Tmax of 6-MAM and morphine was reached within 30 min. All analytes were still detectable at the end of study. This study showed that positive results in urine are expected to be seen shortly after use of heroin in pigs. Detection times were longer than previously indicated, especially for 6-MAM, but previous studies used lower doses. As the physiology of these animals resembles that of the humans, transferability to man is expected.
[Mh] Termos MeSH primário: Heroína/urina
Sus scrofa/urina
[Mh] Termos MeSH secundário: Animais
Cinética
Derivados da Morfina/urina
Detecção do Abuso de Substâncias
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Morphine Derivatives); 70D95007SX (Heroin); M5E47P1ZCH (6-O-monoacetylmorphine); O27Z9CH39A (morphine-3-glucuronide)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170721
[Lr] Data última revisão:
170721
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/jat/bkx017


  7 / 1804 MEDLINE  
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[PMID]:28205234
[Au] Autor:Yadlapalli JSK; Albayati ZAF; Penthala NR; Hendrickson HP; Crooks PA
[Ad] Endereço:Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
[Ti] Título:Stability studies of potent opioid analgesic, morphine-6-O-sulfate in various buffers and biological matrices by HPLC-DAD analysis.
[So] Source:Biomed Chromatogr;31(9), 2017 Sep.
[Is] ISSN:1099-0801
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The 6-O-sulfate ester of morphine (M6S) has previously been shown to be an analgesic with greater potency and fewer side effects than morphine. However, being a sulfate ester derivative of morphine, the question exists as to whether this compound is stable in biological fluids and tissues with regard to pH- and esterase-mediated degradation. To date, no studies have focused on the stability profile of M6S across the physiologically relevant pH range of 1.2-7.4. In addition, the stability of M6S is not known in rat plasma and rat brain homogenate, or in simulated rat gastric and intestinal fluids. This study determines the stability profile of M6S (utilized as the sodium salt) and demonstrates that M6S is highly stable and resilient to either enzymatic- or pH-dependent hydrolysis in vitro.
[Mh] Termos MeSH primário: Analgésicos Opioides/análise
Analgésicos Opioides/química
Cromatografia Líquida de Alta Pressão/métodos
Derivados da Morfina/análise
Derivados da Morfina/química
[Mh] Termos MeSH secundário: Analgésicos Opioides/sangue
Animais
Química Encefálica
Estabilidade de Medicamentos
Suco Gástrico/química
Seres Humanos
Secreções Intestinais/química
Modelos Lineares
Masculino
Modelos Biológicos
Derivados da Morfina/sangue
Ratos
Ratos Sprague-Dawley
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Morphine Derivatives); 0 (morphine-6-O-sulfate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.1002/bmc.3957


  8 / 1804 MEDLINE  
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[PMID]:27925239
[Au] Autor:Noh K; Chen S; Yang QJ; Pang KS
[Ad] Endereço:Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
[Ti] Título:Physiologically based pharmacokinetic modeling revealed minimal codeine intestinal metabolism in first-pass removal in rats.
[So] Source:Biopharm Drug Dispos;38(1):50-74, 2017 Jan.
[Is] ISSN:1099-081X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The physiologically based model with segregated flow to the intestine (SFM-PBPK; partial, lower flow to enterocyte region vs. greater flow to serosal region) was found to describe the first-pass glucuronidation of morphine (M) to morphine-3ß-glucuronide (MG) in rats after intraduodenal (i.d.) and intravenous (i.v.) administration better than the traditional model (TM), for which a single intestinal flow perfused the whole of the intestinal tissue. The segregated flow model (SFM) described a disproportionately greater extent of intestinal morphine glucuronidation for i.d. vs. i.v. administration. The present study applied the same PBPK modeling approaches to examine the contributions of the intestine and liver on the first-pass metabolism of the precursor, codeine (C, 3-methylmorphine) in the rat. Unexpectedly, the profiles of codeine, morphine and morphine-3ß-glucuronide in whole blood, bile and urine, assayed by LCMS, were equally well described by both the TM-PBPK and SFM-PBPK. The fitted parameters for the models were similar, and the net formation intrinsic clearance of morphine (from codeine) for the liver was much higher, being 9- to 13-fold that of the intestine. Simulations, based on the absence of intestinal formation of morphine, correlated well with observations. The lack of discrimination of SFM and TM with the codeine data did not invalidate the SFM-PBPK model but rather suggests that the liver is the only major organ for codeine metabolism. Because of little or no contribution by the intestine to the metabolism of codeine, both the TM- and SFM-PBPK models are equally consistent with the data. Copyright © 2016 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Analgésicos Opioides/farmacocinética
Codeína/farmacocinética
Intestinos/metabolismo
Modelos Biológicos
[Mh] Termos MeSH secundário: Analgésicos Opioides/sangue
Analgésicos Opioides/urina
Animais
Bile/metabolismo
Codeína/sangue
Codeína/urina
Absorção Intestinal
Fígado/metabolismo
Masculino
Morfina/sangue
Morfina/urina
Derivados da Morfina/sangue
Derivados da Morfina/urina
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Morphine Derivatives); 76I7G6D29C (Morphine); O27Z9CH39A (morphine-3-glucuronide); Q830PW7520 (Codeine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170208
[Lr] Data última revisão:
170208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161208
[St] Status:MEDLINE
[do] DOI:10.1002/bdd.2051


  9 / 1804 MEDLINE  
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[PMID]:27915431
[Au] Autor:Staeheli SN; Gascho D; Ebert LC; Kraemer T; Steuer AE
[Ad] Endereço:Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, CH-8057, Zurich, Switzerland.
[Ti] Título:Time-dependent postmortem redistribution of morphine and its metabolites in blood and alternative matrices-application of CT-guided biopsy sampling.
[So] Source:Int J Legal Med;131(2):379-389, 2017 Mar.
[Is] ISSN:1437-1596
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Interpretation of postmortem morphine concentrations in forensic toxicology provides several pitfalls such as missing information on tolerance, analyte stability, or postmortem redistribution (PMR). Recently, it had been shown that computed tomography (CT)-guided collection of biopsies using a robotic arm (virtobot) provides a valuable strategy for systematic studies on time-dependent PMR. Using this technique, time-dependent PMR of morphine and its metabolites was investigated in 12 cases. At admission to the institute (t1), femoral and heart blood (right ventricle) as well as biopsies from the right lung, the right kidney, liver, spleen, and muscle tissue were collected. At autopsy approximately 24 h later (t2), samples from the same body regions were collected again. Additionally, gastric contents, urine, brain tissue, and heart blood from the left ventricle was collected. Morphine, normorphine, hydromorphone, morphine-3-glucuronide, morphine-6-glucuronide, and morphine-sulfate were quantified with LC-MS/MS. In femoral blood, significant increase of morphine concentrations was observed, although ultimately not relevant for forensic interpretation. In the alternative matrices, increases as well as decreases were observed without a clear trend. The morphine metabolites did not exhibit relevant concentration changes. Investigation of underlying redistribution mechanisms indicated that concentration change (i.e., increase) of morphine in femoral blood rather resulted from diffusion processes than from release of morphine from its conjugates. Concentration changes in heart blood might have been caused by redistribution from lung tissue or gastric content. This study also proved that CT-guided collection of biopsies using a virtobot arm is an invaluable tool for future studies on PMR redistribution of other substance groups.
[Mh] Termos MeSH primário: Derivados da Morfina/sangue
Morfina/sangue
Entorpecentes/sangue
Mudanças Depois da Morte
[Mh] Termos MeSH secundário: Biópsia por Agulha Fina
Encéfalo/diagnóstico por imagem
Química Encefálica
Cromatografia Líquida
Conteúdo Gastrointestinal/diagnóstico por imagem
Coração/diagnóstico por imagem
Seres Humanos
Rim/química
Rim/diagnóstico por imagem
Fígado/química
Fígado/diagnóstico por imagem
Pulmão/química
Pulmão/diagnóstico por imagem
Espectrometria de Massas
Morfina/farmacocinética
Derivados da Morfina/farmacocinética
Músculo Esquelético/química
Músculo Esquelético/diagnóstico por imagem
Miocárdio/química
Entorpecentes/farmacocinética
Radiografia Intervencionista
Baço/química
Baço/diagnóstico por imagem
Fatores de Tempo
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Morphine Derivatives); 0 (Narcotics); 76I7G6D29C (Morphine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161205
[St] Status:MEDLINE
[do] DOI:10.1007/s00414-016-1485-2


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[PMID]:27782940
[Au] Autor:Dalesio NM; Hendrix CW; McMichael DH; Thompson CB; Lee CK; Pho H; Arias RS; Lynn RR; Galinkin J; Yaster M; Brown RH; Schwartz AR
[Ad] Endereço:From the *Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; †Department of Otolaryngology/ Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland; ‡Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; §Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; ‖Department of Pharmacy, and Department of Pediatrics, Johns Hopkins Hospital, Baltimore, Maryland ¶Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; and #Department of Anesthesiology, University of Colorado, Aurora, Colorado.
[Ti] Título:Effects of Obesity and Leptin Deficiency on Morphine Pharmacokinetics in a Mouse Model.
[So] Source:Anesth Analg;123(6):1611-1617, 2016 Dec.
[Is] ISSN:1526-7598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Obesity causes multiorgan dysfunction, specifically metabolic abnormalities in the liver. Obese patients are opioid-sensitive and have high rates of respiratory complications after surgery. Obesity also has been shown to cause resistance to leptin, an adipose-derived hormone that is key in regulating hunger, metabolism, and respiratory stimulation. We hypothesized that obesity and leptin deficiency impair opioid pharmacokinetics (PK) independently of one another. METHODS: Morphine PK were characterized in C57BL/6J wild-type (WT), diet-induced obese (DIO), and leptin-deficient (ob/ob) mice, and in ob/ob mice given leptin-replacement (LR) therapy. WT mice received several dosing regimens of morphine. Obese mice (30 g) received one 80 mg/kg bolus of morphine. Blood was collected at fixed times after morphine injection for quantification of plasma morphine and morphine 3-glucuronide (M3G) levels. PK parameters used to evaluate morphine metabolism included area-under the curve (AUC150), maximal morphine concentration (CMAX), and M3G-to-morphine ratio, and drug elimination was determined by clearance (Cl/F), volume of distribution, and half-life (T1/2). PK parameters were compared between mouse groups by the use of 1-way analysis of variance, with P values less than .05 considered significant. RESULTS: DIO compared with WT mice had significantly decreased morphine metabolism with lower M3G-to-morphine ratio (mean difference [MD]: -4.9; 95% confidence interval [CI]: -8.8 to -0.9) as well as a decreased Cl/F (MD: -4.0; 95% CI: -8.9 to -0.03) Ob/ob compared with WT mice had a large increase in morphine exposure with a greater AUC150 (MD: 980.4; 95% CI: 630.1-1330.6), CMAX (MD: 6.8; 95% CI: 2.7-10.9), and longer T1/2 (MD: 23.1; 95% CI: 10.5-35.6), as well as a decreased Cl/F (MD: -7.0; 95% CI: -11.6 to -2.7). Several PK parameters were significantly greater in ob/ob compared with DIO mice, including AUC150 (MD: 636.4; 95% CI: 207.4-1065.4), CMAX (MD: 5.3; 95% CI: 3.2-10.3), and T1/2 (MD: 18.3; 95% CI: 2.8-33.7). When leptin was replaced in ob/ob mice, PK parameters began to approach DIO and WT levels. LR compared with ob/ob mice had significant decreases in AUC150 (MD: -779.9; 95% CI: -1229.8 to -330), CMAX (MD: -6.1; 95% CI: -11.4 to -0.9), and T1/2 (MD: -19; 95% CI: -35.1 to -2.8). Metabolism increased with LR, with LR mice having a greater M3G-to-morphine ratio compared with DIO (MD: 5.3; 95% CI: 0.3-10.4). CONCLUSIONS: Systemic effects associated with obesity decrease morphine metabolism and excretion. A previous study from our laboratory demonstrated that obesity and leptin deficiency decrease the sensitivity of central respiratory control centers to carbon dioxide. Obesity and leptin deficiency substantially decreased morphine metabolism and clearance, and replacing leptin attenuated the PK changes associated with leptin deficiency, suggesting leptin has a direct role in morphine metabolism.
[Mh] Termos MeSH primário: Analgésicos Opioides/farmacocinética
Leptina/deficiência
Morfina/farmacocinética
Obesidade/metabolismo
[Mh] Termos MeSH secundário: Analgésicos Opioides/administração & dosagem
Analgésicos Opioides/sangue
Análise de Variância
Animais
Área Sob a Curva
Dieta Hiperlipídica
Modelos Animais de Doenças
Predisposição Genética para Doença
Meia-Vida
Leptina/genética
Masculino
Taxa de Depuração Metabólica
Camundongos Endogâmicos C57BL
Camundongos Knockout
Camundongos Obesos
Modelos Biológicos
Morfina/administração & dosagem
Morfina/sangue
Derivados da Morfina
Obesidade/sangue
Obesidade/genética
Fenótipo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Leptin); 0 (Morphine Derivatives); 76I7G6D29C (Morphine); O27Z9CH39A (morphine-3-glucuronide)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161027
[St] Status:MEDLINE



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