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1.
J Pharm Pharm Sci ; 18(2): 124-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26158279

RESUMO

PURPOSE: Natural health products (NHPs), including melatonin, are widely used products. Despite the widespread assumption that all NHPs are safe, they contain pharmacologically active substances and can therefore have adverse effects and/or interact with pharmaceuticals. OBJECTIVE: To investigate the mechanism underlying NHP interactions identified through the Pharmacy SONAR active surveillance study. METHODS: Active surveillance was undertaken in community pharmacies to identify adverse events in patients who had recently taken NHPs together with conventional pharmaceuticals. For suspected NHP-pharmaceutical interactions, the possible mechanism of action was explored by in vitro analysis of samples of different products to identify cytochrome P450 enzyme (CYP) inhibition potential. RESULTS: Active surveillance identified a 19-year-old male taking citalopram, nortriptyline and oxycodone concomitantly and who experienced severe sedation when melatonin was added to this regimen. In vitro analysis involving several melatonin products showed product-dependent inhibition of CYP1A2, CYP2C19 and CYP3A7. CONCLUSION: The adverse event was likely due to a primary pharmacokinetic interaction between melatonin and citalopram; although mechanistically, interactions affecting cytochrome P450-mediated metabolism may have occurred with all of these health products. A pharmacodynamic interaction may also be possible, but beyond the capacity of this study to establish.


Assuntos
Inibidores das Enzimas do Citocromo P-450/efeitos adversos , Sedação Profunda/efeitos adversos , Melatonina/efeitos adversos , Conduta Expectante , Administração Oral , Citalopram/administração & dosagem , Citalopram/efeitos adversos , Citalopram/farmacologia , Inibidores das Enzimas do Citocromo P-450/administração & dosagem , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Humanos , Masculino , Melatonina/administração & dosagem , Melatonina/farmacologia , Nortriptilina/administração & dosagem , Nortriptilina/efeitos adversos , Nortriptilina/farmacologia , Oxicodona/administração & dosagem , Oxicodona/efeitos adversos , Oxicodona/farmacologia , Relação Estrutura-Atividade , Adulto Jovem
2.
J Pharm Pharm Sci ; 17(3): 294-301, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25224344

RESUMO

PURPOSE: Thirty-five commercially available Camellia sinensis (black and green) and herbal leisure teas and an assortment of Traditional Chinese medicinal teas were randomly selected and examined for their potential to inhibit the drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4). The study was then extended to examine CYP2D6*1 and CYP2D6*10. METHODS: Microtiter fluorometric assays were utilized to examine the potential for the teas to inhibit CYP-mediated metabolism. Aqueous or alcoholic extracts of the dried tea plant material were examined. METHODS: Most of the black and green leisure teas generally inhibited CYP3A4 more than the Chinese medicinal teas. The medicinal Chinese teas were generally more inhibitory towards CYP3A4 compared to the CYP2D6 isozymes, and the aqueous extracts displayed more potency than the alcoholic extracts. CONCLUSIONS: Tea whether used for leisure or medicinal purposes has the potential to inhibit CYP3A4-mediated drug metabolism particularly black tea.


Assuntos
Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Inibidores das Enzimas do Citocromo P-450/farmacologia , Chá/química , Camellia sinensis/química , Camellia sinensis/metabolismo , Inibidores das Enzimas do Citocromo P-450/química , Inibidores das Enzimas do Citocromo P-450/metabolismo , Medicina Tradicional Chinesa , Relação Estrutura-Atividade , Chá/metabolismo
3.
J Pharm Pharm Sci ; 17(2): 254-65, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24934554

RESUMO

PURPOSE: To study the effect of functional foods on human cytochrome P450 (CYP) and the gut bacterial microflora that may potentially affect drug metabolism and ultimately affect human health and wellness. METHODS: This study examined a variety of food plants from the Apiaceae, Fabaceae, and Lamiaceae families for their inhibitory potential on cytochrome 2D6-, 3A4-, 3A5-, and 3A7-mediated metabolism. The antimicrobial effects of these samples were also investigated with 7 selected bacterial surrogate species to determine potential effects on the gut microflora. RESULTS: The highest CYP inhibitory activities, based upon visual examination, were observed from extracts of celery seed, cumin, fennel seed, basil, oregano, and rosemary belonging to the Apiaceae and Lamiaceae families, respectively. Likewise, the strongest antimicrobial activities were also observed in the Apiaceae and Lamiaceae. No significant antimicrobial and CYP inhibition was observed in the Fabaceae extracts. CONCLUSION: Results demonstrated the possible risk of food-drug interactions from spice and herb plants may affect drug disposition and safety.


Assuntos
Antibacterianos/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Alimento Funcional , Antibacterianos/química , Antibacterianos/isolamento & purificação , Apiaceae/química , Apium/química , Cuminum/química , Inibidores das Enzimas do Citocromo P-450/química , Inibidores das Enzimas do Citocromo P-450/isolamento & purificação , Relação Dose-Resposta a Droga , Foeniculum/química , Humanos , Lamiaceae/química , Testes de Sensibilidade Microbiana , Ocimum basilicum/química , Origanum/química , Sementes/química , Relação Estrutura-Atividade
4.
J Pharm Pharm Sci ; 14(1): 1-16, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21501549

RESUMO

PURPOSE: The use of supplements as herbal and micronutrient natural health products with conventional health products has become increasingly popular. It has been reported that some herbal products can inhibit the activity of cytochrome P450-mediated metabolism and drug disposition. This study was designed to investigate a case report of a severe adverse event to determine the potential interactions of femMED, Thyrosense and vitamins on cytochrome P450-mediated drug metabolism. METHODS: The effect of extracts from these commercially available herbal formulations, trans-ß-carotene, multivitamins, and vitamin D3 supplements on cytochrome P450-mediated drug metabolism of marker substrates was determined in vitro. RESULTS: The blended herbal products femMED and Thyrosense had a high potential to affect the safety and efficacy of many health products. Some vitamin and trans-ß-carotene containing products also have the potential to affect drug disposition. The tBC content of various products was analyzed and significant discrepancies were found among them and between values indicated on product labels. Product extracts also exhibited a low to moderate capacity to inhibit cytochrome P450 2C9, 2C19 and 3A4-mediated metabolism. CONCLUSIONS: The findings of this study suggest that these herbal products and most vitamin products may have an inhibitory effect on cytochrome P450 activity that could contribute to development of an adverse event. Further work is warranted to determine how supplementation with these products may affect drug metabolism in an in vivo context.


Assuntos
Inibidores das Enzimas do Citocromo P-450 , Inibidores Enzimáticos/efeitos adversos , Extratos Vegetais/efeitos adversos , Vitaminas/efeitos adversos , Adulto , Colecalciferol/efeitos adversos , Colecalciferol/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Suplementos Nutricionais , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Extratos Vegetais/farmacologia , Vitaminas/farmacologia , beta Caroteno/efeitos adversos , beta Caroteno/farmacologia
5.
Can J Physiol Pharmacol ; 89(1): 13-23, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21186373

RESUMO

Seventeen Cree antidiabetic medicinal plants were studied to determine their potential to inhibit cytochrome P450 3A4 (CYP3A4) through mechanism-based inactivation (MBI). The ethanolic extracts of the medicinal plants were studied for their inhibition of CYP3A4 using the substrates testosterone and dibenzylfluorescein (DBF) in high pressure liquid chromatography (HPLC) and microtiter fluorometric assays, respectively. Using testosterone as a substrate, extracts of Alnus incana, Sarracenia purpurea, and Lycopodium clavatum were identified as potent CYP3A4 MBIs, while those from Abies balsamea, Picea mariana, Pinus banksiana, Rhododendron tomentosum, Kalmia angustifolia, and Picea glauca were identified as less potent inactivators. Not unexpectedly, the other substrate, DBF, showed a different profile of inhibition. Only A. balsamea was identified as a CYP3A4 MBI using DBF. Abies balsamea displayed both NADPH- and time-dependence of CYP3A4 inhibition using both substrates. Overall, several of the medicinal plants may markedly deplete CYP3A4 through MBI and, consequently, decrease the metabolism of CYP3A4 substrates including numerous medications used by diabetics.


Assuntos
Inibidores do Citocromo P-450 CYP3A , Citocromo P-450 CYP3A/fisiologia , Diabetes Mellitus Tipo 2/enzimologia , Hydrastis , Hipoglicemiantes/farmacologia , Indígenas Norte-Americanos , Extratos Vegetais/farmacologia , Plantas Medicinais/fisiologia , Terapias Complementares/métodos , Horticultura Terapêutica/métodos , Humanos , Hipoglicemiantes/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química , Quebeque , Especificidade por Substrato/efeitos dos fármacos , Especificidade por Substrato/fisiologia
6.
J Pharm Pharm Sci ; 13(1): 43-55, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20456830

RESUMO

PURPOSE: Oseltamivir is a prodrug that requires metabolic activation but there is little information on whether natural health products interact to prevent the biotransformation by the carboxylesterase. METHODS: HPLC-DAD-ESI-MSD and fluorometric assays were used to determine if 50-pooled mixed gender human liver microsomes can mediate the formation of the active carboxylate metabolite and then if this reaction is affected by natural health products. RESULTS: Extracts from 6 traditional Cree botanicals, a commercially available Echinacea product, Goldenseal and a traditional Chinese medicine reduced the formation of the active drug. In addition to oseltamivir carboxylate we report the detection of two new metabolites which are derivatives of oseltamivir carboxylate, one of which is a metabonate formed as a result of methanol. CONCLUSIONS: In vitro studies would suggest that there is the potential for some natural health products used by patients in response to pandemic A/H1N1 to reduce drug efficacy. Further studies are required to determine if these potential interactions could be clinically significant.


Assuntos
Antivirais/metabolismo , Interações Ervas-Drogas , Microssomos Hepáticos/metabolismo , Oseltamivir/análogos & derivados , Produtos Biológicos/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Fluorometria , Humanos , Masculino , Medicina Tradicional Chinesa , Oseltamivir/metabolismo , Extratos Vegetais/farmacologia , Pró-Fármacos , Espectrometria de Massas por Ionização por Electrospray/métodos
7.
J Complement Integr Med ; 13(3): 257-265, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27352447

RESUMO

BACKGROUND: Goji berry (Lycium barbarum) has been used as traditional Chinese medicine and a functional food in China. Goji tea may interact with drugs such as warfarin by inhibiting the cytochrome P450 (CYP) 2C9, and this study was undertaken to characterize the effect of Goji products on CYP2C9/19-, CYP2D6 *1/*10-, CYP3A4/5/7-, CYP19-, and flavin-containing monooxygenase (FMO) 3-mediated metabolism. METHODS: Goji juice, water, and ethanol extracts were examined for their effect on CYP2C9/19-, 2D6-, 3A4/5/7-, 4A11-, CYP19-, and FMO3-mediated metabolism by using in vitro bioassay. The mechanism-based inactivation (MBI) of Goji juice on CYP3A4 was also examined. RESULTS: Data indicates that both fresh juice and commercially available juice caused strong inhibition (over 75 %) of most of the major CYP450 enzymes and moderate inhibition of FMO3 (30-60 %). Compared to juice, the Goji cold/hot water extracts effected low inhibition (below 30 %) of these enzymes. Ethanol (80 %) extracts exhibit the strongest inhibition on CYP2C9 and 2C19 (over 90 %). The inhibition pattern of dried and fresh berry extract and high-performance liquid chromatography (HPLC)-UV fingerprints were similar. CONCLUSIONS: These findings suggest that Goji products (berries, tea, tincture, and juice) can inhibit phase I drug metabolism enzymes and have the potential to affect the safety and efficacy of therapeutic products.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Frutas , Interações Ervas-Drogas , Lycium , Desintoxicação Metabólica Fase I , Oxigenases/metabolismo , Extratos Vegetais/farmacologia , Humanos , Preparações de Plantas
8.
J Ethnopharmacol ; 155(1): 841-6, 2014 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-24971793

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron groenlandicum (Bog Labrador tea), Rhododendron tomentosum (Marsh Labrador tea) and Juniperus communis (Juniper) are used in medicinal teas by Canadian aboriginal cultures alone and in combination with conventional drug products. The safety of this combination had not been previously examined and this study was initiated to examine the potential of medicinal teas to inhibit the major human drug metabolizing enzyme, cytochrome P450 3A4 (CYP3A4). MATERIALS AND METHODS: The decoctions of Rhododendron groenlandicum and Rhododendron tomentosum leaves and Juniperus communis berries were examined in a microtiter fluorometric assay to examine their potential to inhibit CYP-mediated metabolism. RESULTS: The decoctions showed progressive inhibition towards CYP3A4 the longer the leaves or berries were brewed. R. Rhododendron groenlandicum and Juniperus communis may have the potential to inhibit CYP3A4-mediated metabolism. CONCLUSIONS: The findings of this study with these traditional medicines are significant in that they provide mechanistic support that these products have the potential to affect the safety and efficacy of other health and medicinal products. As this study only examined CYP3A4, it is possible that these medicinals contain substances that could also affect other metabolic enzymes.


Assuntos
Citocromo P-450 CYP3A/efeitos dos fármacos , Juniperus/química , Extratos Vegetais/farmacologia , Rhododendron/química , Bebidas , Canadá , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/isolamento & purificação , Inibidores do Citocromo P-450 CYP3A/farmacologia , Fluorometria , Frutas , Humanos , Indígenas Norte-Americanos , Medicina Tradicional , Folhas de Planta , Fatores de Tempo
9.
J Agric Food Chem ; 59(9): 5159-63, 2011 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-21476568

RESUMO

The potential for 15 different ales (6), ciders (2 apple and 1 pear), and porters (6) and 2 non-alcoholic products to affect cytochrome P450 (CYP)-mediated biotransformation and P-glycoprotein-mediated efflux of rhodamine was examined. As in our previous study, a wide range of recovered nonvolatile suspended solids dry weights were noted. Aliquots were also found to have varying effects on biotransformation and efflux. Distinct differences in product ability to affect the safety and efficacy of therapeutic products confirmed our initial findings that some porters (stouts) have a potential to affect the safety and efficacy of health products metabolized by CYP2D6 and CYP3A4 isozymes. Most products, except 2 of the ciders and the 2 non-alcoholic products, also have the potential to affect the safety of CYP2C9 metabolized medications and supplements. Further studies are required to determine the clinical significance of these findings.


Assuntos
Bebidas Alcoólicas/análise , Hidrocarboneto de Aril Hidroxilases/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Humulus/química , Extratos Vegetais/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Citocromo P-450 CYP2C9 , Inibidores do Citocromo P-450 CYP2D6 , Inibidores do Citocromo P-450 CYP3A , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/farmacologia , Humanos , Extratos Vegetais/análise
10.
J Ethnopharmacol ; 128(2): 390-4, 2010 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-20109542

RESUMO

AIM OF THE STUDY: In Africa, medicinal plants are used intensively and concomitantly with allopathic medicines in the treatment of opportunity diseases by many patients or by healthy person to prevent diseases. However, there is little information about the interactions between medicines and botanical products used currently in West Africa area. Therefore, the aim of the present investigation is to study the effect of some plant products on CYP3A4, CYP3A5 and CYP3A7, three individual enzymes of CYP3A subfamily, in vitro. MATERIALS AND METHODS: Teas and ethanolic extracts of medicinal, food and co-administered plants were evaluated on CYP3A4, CYP3A5 and CYP3A7 individual enzymes in vitro using fluorometric assays. RESULTS: Extracts of adjuvant plants such as Aframomum cuspidatum, and Aframomum melegueta, as well as one medicinal plant (Harrisonia abyssinica) inhibited CYP3A4, CYP3A5 and CYP3A7 activity more than 90%. Phyllanthus amarus showed high inhibition of CYP3A5 and CYP3A7. Food plants (Solanum macrocarpon and Talinum triangulare) inhibited CYP3A4 and CYP3A5 less than 20%. CONCLUSION: These results indicate that plants tested in this study affect in vitro the activity of the main three CYP3A subfamily enzymes. These active plants could interfere with the metabolism at phase I of conventional drugs in vivo as well act as pharmacoenhancers in herbal mixtures.


Assuntos
Citocromo P-450 CYP3A/metabolismo , Interações Medicamentosas/genética , Isoenzimas/metabolismo , Preparações Farmacêuticas/metabolismo , Plantas Comestíveis/metabolismo , África , População Negra/genética , Citocromo P-450 CYP3A/genética , Humanos , Isoenzimas/genética , Plantas Comestíveis/genética
11.
J Ethnopharmacol ; 126(1): 119-26, 2009 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-19665535

RESUMO

AIM OF THE STUDY: Cree traditional medicine is commonly used concomitantly with prescribed drugs to treat health problems related to type II diabetes (T2D) that is endemic in the Cree population. However, the safety of traditional Cree medicines with respect to drug metabolism is unknown. MATERIALS AND METHODS: Seventeen anti-diabetic plant extracts were screened for their potential inhibition of 11 isoforms of the drug-metabolizing cytochrome P450s (CYPs), and flavin-containing monooxygenase 3 (FMO3) in fluorometric plate reader assays. Comparative analyses were conducted to determine if particular extracts were more inhibitory, or if particular enzymes were more inhibited. RESULTS: Many anti-diabetic plant extracts inhibited the CYPs, with CYP2C and 3A isoforms being most prone to inhibition. The order of inhibition for the enzymes by the Cree plant extracts was: 2C19>3A7>3A5>3A4>2C9>2C8>FMO3>1A2>2E1>19>2D6>2B6. Extracts from Rhododendron groenlandicum, Sorbus decora, and Kalmia angustifolia were identified as having strong inhibition towards many CYP isoforms. CONCLUSION: These findings demonstrate that extracts from most plant species examined have the potential to affect CYP2C- and 3A4-mediated metabolism, and have the potential to affect the bioavailability and pharmacokinetics of conventional and traditional medicines during concomitant use.


Assuntos
Inibidores das Enzimas do Citocromo P-450 , Hipoglicemiantes/farmacologia , Isoenzimas/antagonistas & inibidores , Medicina Tradicional , Oxigenases/antagonistas & inibidores , Extratos Vegetais/farmacologia , Humanos , Técnicas In Vitro , Indígenas Norte-Americanos , Extratos Vegetais/química
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