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[PMID]:28893642
[Au] Autor:Jiang B; Meng L; Zhang F; Jin X; Zhang G
[Ad] Endereço:Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: Lucid1227@163.com.
[Ti] Título:Enzyme-inducing effects of berberine on cytochrome P450 1A2 in vitro and in vivo.
[So] Source:Life Sci;189:1-7, 2017 Nov 15.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Berberine (BER) is an important anti-bacterial drug from Chinese herbal medicine and a novel drug candidate for preclinical development in recent years. Here we provide evidence that the effects of berberine on cytochrome P450 (CYP) 1A2 in vitro and in vivo. MAIN METHODS: Real-time polymerase chain reaction and western blotting analysis were employed to evaluate the CYP1A2 mRNA levels and protein expression. The enzyme activity was assessed by the metabolic rate of phenacetin to acetaminophen by LC-MS/MS method. KEY FINDINGS: The results indicated that the CYP1A2 mRNA expression and enzyme activity in HepG2 cells after treated with BER (4.5µg/ml) exhibited a significant induction (16.11-fold and 5.0-fold, respectively), which was consistent with those on rat liver microsomes (4.5-fold and 1.98-fold, respectively) by BER induction (10mg/kg/day, i.p.) ex vivo. Beside, BER induced CYP1A2 activity with increases in AUC and C of acetaminophen and the Ke and t of phenacetin after oral administration of phenacetin (p<0.05) in vivo. SIGNIFICANCE: This study firstly reported the induction effect of BER on rats CYP1A2 by intraperitoneal route. But, BER didn't show significant induction effect on CYP1A2 by high-dose orally administrating to rats for 6 consecutive days due to the extremely low bioavailability. The potential drug-drug interactions were supposed to happen when the liver exposed to high dose of BER in vivo by changing administration route.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Berberina/farmacologia
Citocromo P-450 CYP1A2/efeitos dos fármacos
Indução Enzimática/efeitos dos fármacos
Fenacetina/farmacocinética
[Mh] Termos MeSH secundário: Acetaminofen/farmacocinética
Animais
Área Sob a Curva
Western Blotting
Cromatografia Líquida/métodos
Citocromo P-450 CYP1A2/biossíntese
Meia-Vida
Células Hep G2
Seres Humanos
Masculino
Microssomos Hepáticos/efeitos dos fármacos
Microssomos Hepáticos/metabolismo
RNA Mensageiro/metabolismo
Ratos
Ratos Wistar
Reação em Cadeia da Polimerase em Tempo Real
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (RNA, Messenger); 0I8Y3P32UF (Berberine); 362O9ITL9D (Acetaminophen); EC 1.14.14.1 (Cytochrome P-450 CYP1A2); ER0CTH01H9 (Phenacetin)
[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:170913
[St] Status:MEDLINE


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[PMID]:28254952
[Au] Autor:Jilek JL; Tian Y; Yu AM
[Ad] Endereço:Department of Biochemistry and Molecular Medicine, Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, California (J.L.J., Y.T., A.-M.Y.); and Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China (Y.T.).
[Ti] Título:Effects of MicroRNA-34a on the Pharmacokinetics of Cytochrome P450 Probe Drugs in Mice.
[So] Source:Drug Metab Dispos;45(5):512-522, 2017 May.
[Is] ISSN:1521-009X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:MicroRNAs (miRNAs or miRs), including miR-34a, have been shown to regulate nuclear receptor, drug-metabolizing enzyme, and transporter gene expression in various cell model systems. However, to what degree miRNAs affect pharmacokinetics (PK) at the systemic level remains unknown. In addition, miR-34a replacement therapy represents a new cancer treatment strategy, although it is unknown whether miR-34a therapeutic agents could elicit any drug-drug interactions. To address this question, we refined a practical single-mouse PK approach and investigated the effects of a bioengineered miR-34a agent on the PK of several cytochrome P450 probe drugs (midazolam, dextromethorphan, phenacetin, diclofenac, and chlorzoxazone) administered as a cocktail. This approach involves manual serial blood microsampling from a single mouse and requires a sensitive liquid chromatography-tandem mass spectrometry assay, which was able to illustrate the sharp changes in midazolam PK by ketoconazole and pregnenolone 16 -carbonitrile as well as phenacetin PK by -naphthoflavone and 3-methylcholanthrene. Surprisingly, 3-methylcholanthrene also decreased systemic exposure to midazolam, whereas both pregnenolone 16 -carbonitrile and 3-methylcholanthrene largely reduced the exposure to dextromethorphan, diclofenac, and chlorzoxazone. Finally, the biologic miR-34a agent had no significant effects on the PK of cocktail drugs but caused a marginal (45%-48%) increase in systemic exposure to midazolam, phenacetin, and dextromethorphan in mice. In vitro validation of these data suggested that miR-34a slightly attenuated intrinsic clearance of dextromethorphan. These findings from single-mouse PK and corresponding mouse liver microsome models suggest that miR-34a might have minor or no effects on the PK of coadministered cytochrome P450-metabolized drugs.
[Mh] Termos MeSH primário: Sistema Enzimático do Citocromo P-450/metabolismo
MicroRNAs/farmacologia
[Mh] Termos MeSH secundário: Animais
Clorzoxazona/farmacocinética
Inibidores das Enzimas do Citocromo P-450/farmacologia
Dextrometorfano/farmacocinética
Diclofenaco/farmacocinética
Interações Medicamentosas
Masculino
Camundongos
Midazolam/farmacocinética
Farmacocinética
Fenacetina/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytochrome P-450 Enzyme Inhibitors); 0 (MIRN34 microRNA, mouse); 0 (MicroRNAs); 144O8QL0L1 (Diclofenac); 7355X3ROTS (Dextromethorphan); 9035-51-2 (Cytochrome P-450 Enzyme System); ER0CTH01H9 (Phenacetin); H0DE420U8G (Chlorzoxazone); R60L0SM5BC (Midazolam)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170518
[Lr] Data última revisão:
170518
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE
[do] DOI:10.1124/dmd.116.074344


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[PMID]:27860349
[Au] Autor:Ladroue V; Dujourdy L; Besacier F; Jame P
[Ad] Endereço:Institut National de Police Scientifique, Laboratoire de Lyon, 31 avenue Franklin Roosevelt, 69134, Ecully Cedex, France.
[Ti] Título:IRMS to study a common cocaine cutting agent: phenacetin.
[So] Source:Drug Test Anal;9(3):479-484, 2017 Mar.
[Is] ISSN:1942-7611
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Phenacetin is a pharmaceutical closely related to acetaminophen that has been banned in France for a long time due to its nephritic and carcinogenic adverse effects. It frequently appears in cocaine seizures as a cutting agent. Following both sanitary and intelligence motivations, this molecule was chosen for this study, and stable isotopes seemed to be the most appropriate tool. A total of 228 seized samples were collected over a 6-year period, and 8 standards of known origin were purchased. They were submitted to gas chromatography (GC) or elemental analysis - isotope ratio mass spectrometry (EA-IRMS) measurements, depending on their complexity. Stable isotope ratios of carbon, hydrogen, and nitrogen for a part of the sample set, were acquired. The isotopic values of phenacetin standards acquired from various providers located worldwide are quite spread, which indicates that stable isotopes could be used to discriminate manufacturers. However, the measured values of most of the seized samples are concentrated in a narrow range, tending to demonstrate that phenacetin is smuggled from a single source or similar ones. Consequently, stable isotopes could only be used to exclude that several samples come from a common source. Copyright © 2016 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Analgésicos não Entorpecentes/química
Cocaína/química
Inibidores da Captação de Dopamina/química
Fenacetina/química
Drogas Ilícitas/química
[Mh] Termos MeSH secundário: Analgésicos não Entorpecentes/análise
Isótopos de Carbono/análise
Cromatografia Gasosa/métodos
Espectrometria de Massas/métodos
Fenacetina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Non-Narcotic); 0 (Carbon Isotopes); 0 (Dopamine Uptake Inhibitors); 0 (Street Drugs); ER0CTH01H9 (Phenacetin); I5Y540LHVR (Cocaine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE
[do] DOI:10.1002/dta.2137


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[PMID]:27814951
[Au] Autor:Gumbi BP; Moodley B; Birungi G; Ndungu PG
[Ad] Endereço:University of KwaZulu-Natal, School of Chemistry and Physics, Private Bag x 54001, Durban 4000, South Africa.
[Ti] Título:Detection and quantification of acidic drug residues in South African surface water using gas chromatography-mass spectrometry.
[So] Source:Chemosphere;168:1042-1050, 2017 Feb.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A method was optimized for derivatization, separation, detection and quantification of salicylic acid, acetylsalicylic acid, nalidixic acid, ibuprofen, phenacetin, naproxen, ketoprofen, meclofenamic acid and diclofenac in surface water using gas chromatography-mass spectrometry. For most of the acidic drugs, recovery was in the range 60-110% and the percent standard deviation was below 15% for the entire method, with limits of detection ranging from 0.041 to 1.614 µg L . The developed method was applied in the analysis of acidic drugs in Umgeni River system, KwaZulu-Natal South Africa. All of the selected acidic drugs were detected and quantified, their concentration in Umgeni River system ranged from 0.0200 to 68.14 µg L .
[Mh] Termos MeSH primário: Poluentes Químicos da Água/análise
[Mh] Termos MeSH secundário: Ácidos Carbocíclicos/análise
Aspirina/análise
Monitoramento Ambiental
Cromatografia Gasosa-Espectrometria de Massas/métodos
Concentração de Íons de Hidrogênio
Ácido Nalidíxico/análise
Naproxeno/análise
Fenacetina/análise
Rios/química
África do Sul
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acids, Carbocyclic); 0 (Water Pollutants, Chemical); 059QF0KO0R (Water); 3B91HWA56M (Nalidixic Acid); 57Y76R9ATQ (Naproxen); ER0CTH01H9 (Phenacetin); R16CO5Y76E (Aspirin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161106
[St] Status:MEDLINE


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[PMID]:27794450
[Au] Autor:Chitrangi S; Nair P; Khanna A
[Ad] Endereço:Department of Biological Sciences, Sunandan Divatia School of Science, SVKM'S NMIMS (Deemed-to-be ) University, V. L Mehta road, Vile Parle (West), Mumbai 400056, Maharashtra, India.
[Ti] Título:3D engineered In vitro hepatospheroids for studying drug toxicity and metabolism.
[So] Source:Toxicol In Vitro;38:8-18, 2017 Feb.
[Is] ISSN:1879-3177
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Drug toxicity is one of the reasons for late stage drug attrition, because of hepatotoxicity. Various in vitro liver models like primary human hepatocytes, immortalized human hepatic cell lines, liver slices and microsomes have been used; but limited by viability, hepatic gene expression and function. The 3D-engineered construct of hepatocyte-like-cells (HLCs) differentiated from stem cells, may provide a limitless source of hepatocytes with improved reproducibility. Towards this end, we used hepatospheroids (diameter=50-80µm) differentiated from human-umbilical-cord-mesenchymal stem cells (hUC-MSCs) on 3D scaffold GEVAC (Gelatin-vinyl-acetate-copolymer) as in vitro model for studying drug metabolism/toxicity. Our data demonstrated that hUC-MSCs-derived-hepatospheroids cultured on GEVAC expressed significantly higher drug-metabolizing enzymes (CYPs) both at mRNA and activity level compared to 2D culture, using HR-LC/MS. We further showed that hepatospheroids convert phenacetin (by CYP1A2) and testosterone (by CYP3A4) to their human-specific metabolites acetaminophen and 6ß-hydroxytestosterone with a predictive clearance rate of 0.011ml/h/10 cells and 0.021ml/h/10 cells respectively, according to first-order kinetics. Hepatotoxicity was confirmed by exposing hepatospheroids to ethanol and acetaminophen; ROS generation, cell viability, cytoskeleton structure, elevation of liver function enzymes, i.e. AST and ALT, was analyzed. To the best of our knowledge, this is the first report to use hUC-MSCs-derived-hepatospheroids on GEVAC as in vitro model for drug metabolism/toxicity study; which can replace the conventional 2D-models used in drug development.
[Mh] Termos MeSH primário: Técnicas de Cultura de Células
Avaliação Pré-Clínica de Medicamentos/métodos
Hepatócitos
Células Mesenquimais Estromais/citologia
Esferoides Celulares
Cordão Umbilical/citologia
[Mh] Termos MeSH secundário: Células Cultivadas
Sistema Enzimático do Citocromo P-450/genética
Sistema Enzimático do Citocromo P-450/metabolismo
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
Gelatina
Células Hep G2
Hepatócitos/efeitos dos fármacos
Hepatócitos/metabolismo
Seres Humanos
Preparações Farmacêuticas/metabolismo
Fenacetina/farmacologia
Polímeros
Espécies Reativas de Oxigênio/metabolismo
Esferoides Celulares/efeitos dos fármacos
Esferoides Celulares/metabolismo
Testosterona/farmacologia
Compostos de Vinila
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pharmaceutical Preparations); 0 (Polymers); 0 (Reactive Oxygen Species); 0 (Vinyl Compounds); 3XMK78S47O (Testosterone); 9000-70-8 (Gelatin); 9035-51-2 (Cytochrome P-450 Enzyme System); ER0CTH01H9 (Phenacetin); L9MK238N77 (vinyl acetate)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170330
[Lr] Data última revisão:
170330
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161031
[St] Status:MEDLINE


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[PMID]:27285124
[Au] Autor:Nelson LJ; Morgan K; Treskes P; Samuel K; Henderson CJ; LeBled C; Homer N; Grant MH; Hayes PC; Plevris JN
[Ad] Endereço:Hepatology Laboratory, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, UK.
[Ti] Título:Human Hepatic HepaRG Cells Maintain an Organotypic Phenotype with High Intrinsic CYP450 Activity/Metabolism and Significantly Outperform Standard HepG2/C3A Cells for Pharmaceutical and Therapeutic Applications.
[So] Source:Basic Clin Pharmacol Toxicol;120(1):30-37, 2017 Jan.
[Is] ISSN:1742-7843
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Conventional in vitro human hepatic models for drug testing are based on the use of standard cell lines derived from hepatomas or primary human hepatocytes (PHHs). Limited availability, interdonor functional variability and early phenotypic alterations in PHHs restrict their use, whilst standard cell lines such as HepG2 lack a substantial and variable set of liver-specific functions such as CYP450 activity. Alternatives include the HepG2-derivative C3A cells selected as a more differentiated and metabolically active hepatic phenotype. Human HepaRG cells are an alternative organotypic co-culture model of hepatocytes and cholangiocytes reported to maintain in vivo-like liver-specific functions, including intact Phase I-III drug metabolism. In this study, we compared C3A and human HepaRG cells using phenotypic profiling, CYP450 activity and drug metabolism parameters to assess their value as hepatic models for pre-clinical drug testing or therapeutics. Compared with C3As, HepaRG co-cultures exhibit a more organotypic phenotype, including evidence of hepatic polarity with the strong expression of CYP3A4, the major isoform involved in the metabolism of over 60% of marketed drugs. Significantly greater CYP450 activity and expression of CYP1A2, CYP2E1 and CYP3A4 genes in HepaRG cells (comparable with that of human liver tissue) was demonstrated. Moreover, HepaRG cells also preferentially expressed the hepatic integrin α ß - an important modulator of cell behaviour including growth and survival, differentiation and polarity. Drug metabolite profiling of phenacetin (CYP1A2) and testosterone (CYP3A4) using LC-MS/MS and HPLC, respectively, revealed that HepaRGs had more intact (Phase I-II) metabolism profile. Thus, HepaRG cells significantly outperform C3A cells for the potential pharmaceutical and therapeutic applications.
[Mh] Termos MeSH primário: Sistema Enzimático do Citocromo P-450/metabolismo
Avaliação Pré-Clínica de Medicamentos/métodos
Regulação Enzimológica da Expressão Gênica
Hepatócitos/enzimologia
[Mh] Termos MeSH secundário: Alternativas aos Testes com Animais
Ductos Biliares/citologia
Ductos Biliares/enzimologia
Ductos Biliares/metabolismo
Diferenciação Celular
Linhagem Celular
Técnicas de Cocultura
Sistema Enzimático do Citocromo P-450/genética
Células Epiteliais/enzimologia
Células Epiteliais/metabolismo
Células Hep G2
Hepatócitos/citologia
Hepatócitos/metabolismo
Seres Humanos
Desentoxicação Metabólica Fase I
Desintoxicação Metabólica Fase II
Fenacetina/metabolismo
Testosterona/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
3XMK78S47O (Testosterone); 9035-51-2 (Cytochrome P-450 Enzyme System); ER0CTH01H9 (Phenacetin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160611
[St] Status:MEDLINE
[do] DOI:10.1111/bcpt.12631


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[PMID]:27452991
[Au] Autor:Li Y; Wang J; Zhan L; Wleklinski M; Wang J; Xiong C; Liu H; Zhou Y; Nie Z
[Ad] Endereço:Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, China; Beijing National Laboratory for Molecular Sciences, Beijing 100190, China.
[Ti] Título:The bridge between thin layer chromatography-mass spectrometry and high-performance liquid chromatography-mass spectrometry: The realization of liquid thin layer chromatography-mass spectrometry (LTLC-MS).
[So] Source:J Chromatogr A;1460:181-9, 2016 Aug 19.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The combination of thin layer chromatography (TLC) and mass spectrometry (MS) has been studied for decades, but for most cases MS detection is done after TLC separation is finished. Here, an online simultaneous TLC-MS analysis system, liquid thin layer chromatography-mass spectrometry (LTLC-MS), is developed which successfully synchronize TLC separation process and MS detection process like GC-MS and HPLC-MS do. And there's no need to use specially designed TLC, just regular TLC plates are enough. LTLC-MS method is composed of a newly developed ambient ionization method, glow discharge-matrix assisted infrared desorption ionization (GD-MAIRDI), and forced-flow TLC (FFTLC) technique, which guarantees the MS detection process does not disturb the TLC separation process throughout the whole analysis. The whole LTLC-MS analysis only need two steps and less than 15min. Mixtures as well as the two main components of a pain relief pills have been successfully analyzed by LTLC-MS. This proof of concept study opens up new possibilities of combining TLC with MS, and will further broaden the application abilities of TLC.
[Mh] Termos MeSH primário: Analgésicos/análise
Cromatografia Líquida de Alta Pressão/métodos
Cromatografia em Camada Delgada/métodos
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
[Mh] Termos MeSH secundário: Aminopirina/análise
Analgésicos/química
Cromatografia Líquida de Alta Pressão/instrumentação
Cromatografia em Camada Delgada/instrumentação
Fenacetina/análise
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/instrumentação
Comprimidos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics); 0 (Tablets); 01704YP3MO (Aminopyrine); ER0CTH01H9 (Phenacetin)
[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:160726
[St] Status:MEDLINE


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[PMID]:27318879
[Au] Autor:Haraya K; Kato M; Chiba K; Sugiyama Y
[Ad] Endereço:Chugai Pharmabody Research Pte. Ltd., Singapore. Electronic address: haraya.kenta@chugai-pharm.co.jp.
[Ti] Título:Prediction of inter-individual variability on the pharmacokinetics of CYP1A2 substrates in non-smoking healthy volunteers.
[So] Source:Drug Metab Pharmacokinet;31(4):276-84, 2016 Aug.
[Is] ISSN:1880-0920
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The activity of CYP1A2, a major drug-metabolizing enzyme, is known to be affected by various environmental factors. Our study aimed to predict inter-individual variability of AUC/Dose of CYP1A2 substrates in non-smoking healthy volunteers using the Monte Carlo simulation. Inter-individual variability in hepatic intrinsic clearance of CYP1A2 substrates (CLint,h,1A2) was estimated using dispersion model based on the inter-individual variability (N = 96) of the AUC of caffeine, a major CYP1A2 substrate. The estimated coefficient of variation (CV) of CLint,h,1A2 was 55%, similar to previously reported CLint,h,2D6 (60%) but larger than CLint,h,3A4 (33%). Then, this estimated CV was validated by predicting the CVs of AUC/Dose of tizanidine and phenacetin, which are mainly metabolized by CYP1A2 and have negligible renal clearance. As a result, reported CVs were successfully predicted within 2.5-97.5 percentile range of predicted values. Moreover, CVs for AUC/Dose of the CYP1A2 substrates theophylline and lidocaine, which are affected by other CYPs and renal clearance, were also successfully predicted. The inter-individual variability of AUC/Dose of CYP1A2 substrates was successfully predicted using 55% CV for CLint,h,1A2, and the results, along with those reported by our group for other CYPs, support the prediction of inter-individual variability of pharmacokinetics in the clinical setting.
[Mh] Termos MeSH primário: Citocromo P-450 CYP1A2/metabolismo
[Mh] Termos MeSH secundário: Área Sob a Curva
Cafeína/farmacocinética
Clonidina/análogos & derivados
Clonidina/farmacocinética
Voluntários Saudáveis
Seres Humanos
Lidocaína/farmacocinética
Método de Monte Carlo
Fenacetina/farmacocinética
Teofilina/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
3G6A5W338E (Caffeine); 6AI06C00GW (tizanidine); 98PI200987 (Lidocaine); C137DTR5RG (Theophylline); EC 1.14.14.1 (CYP1A2 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP1A2); ER0CTH01H9 (Phenacetin); MN3L5RMN02 (Clonidine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170327
[Lr] Data última revisão:
170327
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160620
[St] Status:MEDLINE


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[PMID]:27037683
[Au] Autor:Jellali R; Bricks T; Jacques S; Fleury MJ; Paullier P; Merlier F; Leclerc E
[Ad] Endereço:Sorbonne universités, Université de Technologie de Compiègne, CNRS, UMR, 7338, Biomécanique et Bioingénierie, Centre de recherche Royallieu, 60203, Compiègne cedex, France.
[Ti] Título:Long-term human primary hepatocyte cultures in a microfluidic liver biochip show maintenance of mRNA levels and higher drug metabolism compared with Petri cultures.
[So] Source:Biopharm Drug Dispos;37(5):264-75, 2016 Jul.
[Is] ISSN:1099-081X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Human primary hepatocytes were cultivated in a microfluidic bioreactor and in Petri dishes for 13 days. mRNA kinetics in biochips showed an increase in the levels of CYP2B6, CYP2C19, CYP2C8, CYP3A4, CYP1A2, CYP2D6, HNF4a, SULT1A1, UGT1A1 mRNA related genes when compared with post extraction levels. In addition, comparison with Petri dishes showed higher levels of CYP2B6, CYP2C19, CYP2C8, CYP3A4, CYP1A2, CYP2D6 related genes at the end of culture. Functional assays illustrated a higher urea and albumin production over the period of culture in biochips. Bioreactor drug metabolism (midazolam and phenacetin) was not superior to the Petri dish after 2 days of culture. The CYP3A4 midazolam metabolism was maintained in biochips after 13 days of culture, whereas it was almost undetectable in Petri dishes. This led to a 5000-fold higher value of the metabolic ratio in the biochips. CYP1A2 phenacetin metabolism was found to be higher in biochips after 5, 9 and 13 days of culture. Thus, a 100-fold higher metabolic ratio of APAP in biochips was measured after 13 days of perfusion. These results demonstrated functional primary human hepatocyte culture in the bioreactor in a long-term culture. Copyright © 2016 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Hepatócitos/metabolismo
Dispositivos Lab-On-A-Chip
RNA Mensageiro/metabolismo
[Mh] Termos MeSH secundário: Albuminas/análise
Arilsulfotransferase/genética
Arilsulfotransferase/metabolismo
Reatores Biológicos
Sobrevivência Celular
Células Cultivadas
Sistema Enzimático do Citocromo P-450/genética
Sistema Enzimático do Citocromo P-450/metabolismo
Glucose/metabolismo
Glucuronosiltransferase/genética
Glucuronosiltransferase/metabolismo
Fator 4 Nuclear de Hepatócito/genética
Fator 4 Nuclear de Hepatócito/metabolismo
Seres Humanos
Fígado/metabolismo
Midazolam/farmacologia
Fenacetina/farmacologia
Ureia/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Albumins); 0 (HNF4A protein, human); 0 (Hepatocyte Nuclear Factor 4); 0 (RNA, Messenger); 8W8T17847W (Urea); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 2.4.1.- (UGT1A1 enzyme); EC 2.4.1.17 (Glucuronosyltransferase); EC 2.8.2.1 (Arylsulfotransferase); EC 2.8.2.1 (SULT1A1 protein, human); ER0CTH01H9 (Phenacetin); IY9XDZ35W2 (Glucose); R60L0SM5BC (Midazolam)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170127
[Lr] Data última revisão:
170127
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160403
[St] Status:MEDLINE
[do] DOI:10.1002/bdd.2010


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AUGUSTI, Rodinei
Texto completo
[PMID]:26970868
[Au] Autor:De Carvalho TC; Tosato F; Souza LM; Santos H; Merlo BB; Ortiz RS; Rodrigues RR; Filgueiras PR; França HS; Augusti R; Romão W; Vaz BG
[Ad] Endereço:Instituto de Química, Universidade Federal de Goiás, 74001-970 Goiânia, GO, Brazil.
[Ti] Título:Thin layer chromatography coupled to paper spray ionization mass spectrometry for cocaine and its adulterants analysis.
[So] Source:Forensic Sci Int;262:56-65, 2016 May.
[Is] ISSN:1872-6283
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Thin layer chromatography (TLC) is a simple and inexpensive type of chromatography that is extensively used in forensic laboratories for drugs of abuse analysis. In this work, TLC is optimized to analyze cocaine and its adulterants (caffeine, benzocaine, lidocaine and phenacetin) in which the sensitivity (visual determination of LOD from 0.5 to 14mgmL(-1)) and the selectivity (from the study of three different eluents: CHCl3:CH3OH:HCOOHglacial (75:20:5v%), (C2H5)2O:CHCl3 (50:50v%) and CH3OH:NH4OH (100:1.5v%)) were evaluated. Aiming to improve these figures of merit, the TLC spots were identified and quantified (linearity with R(2)>0.98) by the paper spray ionization mass spectrometry (PS-MS), reaching now lower LOD values (>1.0µgmL(-1)). The method developed in this work open up perspective of enhancing the reliability of traditional and routine TLC analysis employed in the criminal expertise units. Higher sensitivity, selectivity and rapidity can be provided in forensic reports, besides the possibility of quantitative analysis. Due to the great simplicity, the PS(+)-MS technique can also be coupled directly to other separation techniques such as the paper chromatography and can still be used in analyses of LSD blotter, documents and synthetic drugs.
[Mh] Termos MeSH primário: Cocaína/química
Contaminação de Medicamentos
Entorpecentes/química
[Mh] Termos MeSH secundário: Benzocaína/análise
Cafeína/análise
Cromatografia em Camada Delgada
Seres Humanos
Lidocaína/análise
Espectrometria de Massas/métodos
Fenacetina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Narcotics); 3G6A5W338E (Caffeine); 98PI200987 (Lidocaine); ER0CTH01H9 (Phenacetin); I5Y540LHVR (Cocaine); U3RSY48JW5 (Benzocaine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170202
[Lr] Data última revisão:
170202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160314
[St] Status:MEDLINE



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