RESUMEN
Toxic metals are one of the significant groups of chemical contaminants that humans are exposed to by oral, inhalation, and dermal routes. Exposure to these chemicals begins with intrauterine life and continues during lactation period at the first years of life. Breastfeeding has a much more special place than other nutrition options for infants. However, when possibility of contaminant transfer by breast milk is considered, its safety and quality is essential. Regarding infant and mother health and limited number of information on this field in Turkey, measuring contamination levels in breast milk is important. Therefore, in the present study, lead (Pb), cadmium (Cd), nickel (Ni), and arsenic (As) levels were measured by atomic absorption spectrometry in 64 breast milk samples obtained from mothers from Ankara, Turkey. Pb and Ni levels in breast milk samples were found to be 391.45±269.01 µg/l and 43.94±33.82 µg/l (mean ± SD), respectively. Cd was found only in one of 64 samples, and the level was 4.62 µg/l. As level was below the limit of quantification (LOQ, 7.6 µg/l) in all samples. These findings will accurately direct strategies and solutions of protection against contaminants in order to reduce their levels in biological fluids.
Asunto(s)
Arsénico/análisis , Cadmio/análisis , Plomo/análisis , Leche Humana/química , Níquel/análisis , Arsénico/química , Cadmio/química , Monitoreo del Ambiente/métodos , Contaminantes Ambientales/análisis , Contaminantes Ambientales/química , Femenino , Humanos , Lactancia , Plomo/química , Límite de Detección , Níquel/química , Espectrofotometría Atómica , TurquíaRESUMEN
This study aimed to investigate a food effect on the bio-availability of modified-release (MR) trimetazidine tablets in 36 healthy volunteers. Trimetazidine, an anti-ischemic drug, protects the myocardial cell from the harmful effects of ischemia. The authors investigated the effect of being under a fasting or fed state at the time of drug intake on the bioavailability of trimetazidine 35-mg MR tablets in a randomized, open-label, crossover, 2-arm, 4-period, 2-sequence bioequivalence study design with a 14-day washout period. Plasma concentration of trimetazidine was assayed in timed samples with a validated high- performance liquid chromatography/mass selective detector that had a lower limit of quantification of 2.5 ng/mL. Test and reference formulations gave a mean trimetazidine C(max) of 63.26 ng/mL and 69.18 ng/mL for the fasting state and 64.19 ng/mL and 63.11 ng/mL for the fed state, respectively. The AUC(0-tlast) mean of trimetazidine was 726.31 ng·h/mL and 733.01 ng·h/mL for the fasting state and 706.40 ng·h/mL and 691.40 ng·h/mL for the fed state for test/reference formulations. There were no significant differences in pharmacokinetic parameters between the 2 formulations and the fasting/fed states. The authors showed that there is no food effect and no need for a 4-period study to evaluate the bioequivalence of trimetazidine MR tablets.
Asunto(s)
Interacciones Alimento-Droga , Trimetazidina/farmacocinética , Vasodilatadores/farmacocinética , Adulto , Disponibilidad Biológica , Desayuno , Estudios Cruzados , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Ayuno/metabolismo , Humanos , Masculino , Comprimidos , Equivalencia Terapéutica , Trimetazidina/administración & dosificación , Trimetazidina/sangre , Vasodilatadores/administración & dosificación , Vasodilatadores/sangre , Adulto JovenRESUMEN
The carboxylic acid group of the anti-inflammatory drug, (S)-2-(6-methoxynaphthalen-2-yl) propanoic acid, naproxen (CAS 22204-53-1) was reacted with the substituted ethylamine derivatives to form (S)-2-(6-methoxynaphthalen-2-yl)-N-substituted ethyl propanamides by using N,N'-dicyclohexyl carbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP). Anti-inflammatory and analgesic activities of the compounds were assessed in vivo by carrageenan-induced hind paw edema and p-benzoquinone induced abdominal contraction tests in mice, respectively. In addition, the ulcerogenic properties of the new compounds were evaluated, and compared to that of naproxen. Among the newly synthesized compounds, compound 2f showed the highest analgesic and antiinflammatory activity at 100 mg/kg oral dose, without inducing any gastric lesion. Although this compound induced less gastric lesions than naproxen, it was found to have less anti-inflammatory and analgesic activity when compared to indometacin (CAS 53-86-1). These new compounds therefore deserve further attention to develop new lead drugs.
Asunto(s)
Amidas/síntesis química , Amidas/farmacología , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/farmacología , Naftalenos/síntesis química , Naftalenos/farmacología , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Benzoquinonas , Carragenina , Sistemas de Liberación de Medicamentos , Diseño de Fármacos , Edema/inducido químicamente , Edema/patología , Edema/prevención & control , Pie/patología , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Ratones , Naproxeno/efectos adversos , Naproxeno/farmacología , Dolor/inducido químicamente , Dolor/prevención & control , Espectrofotometría Infrarroja , Úlcera Gástrica/inducido químicamente , Relación Estructura-ActividadRESUMEN
Flurbiprofen (CAS 5104-49-4) is a member of phenylalkanoic acid derivative group of nonsteroid anti-inflammatory drugs. It exhibits anti-inflammatory, analgesic and antipyretic activities. Two different tablets containing flurbiprofen (FLU) were investigated in 24 healthy volunteers to prove the bioequivalence between both treatments after single oral dose administrations. Fluroben 100 mg tablet and 100 mg tablet of the originator product were used as test and reference preparation respectively. The study was performed open label, randomized, two period cross-over design with 15 days wash out period. Blood samples were taken up to 24 hours for pharmacokinetic profiling. The plasma concentrations of flurbiprofen were determined with validated HPLC-UV method. Maximum plasma concentration (Cmax) of FLU 19,143.65 ng/ml and 19,164.22 ng/ml were found for test and reference formulation respectively. Areas under the plasma concentration time curve AUC(0-infinity), of 118 501.4 ng.h/ml and 111,339.8 ng.h/ml were calculated test and reference formulation respectively. Primary target parameters AUC (0-infinity) and Cmax, both of them were tested parametrically by analysis of variance (ANOVA); 90% confidence intervals were between 100.5%-111.18% for AUC(0-infinity), and 87.6%-115.0% for Cmax. All these values were within the acceptance range (80%-125%) for bioequivalence studies.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Flurbiprofeno/administración & dosificación , Flurbiprofeno/uso terapéutico , Adolescente , Adulto , Antiinflamatorios no Esteroideos/farmacocinética , Área Bajo la Curva , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Método Doble Ciego , Flurbiprofeno/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Espectrofotometría Ultravioleta , Comprimidos , Equivalencia Terapéutica , Adulto JovenRESUMEN
Clarithromycin is a broad-spectrum macrolide antibacterial agent which is effective both in vitro and in vivo against the major pathogens responsible for respiratory tract infections. Clarithromycin's principal metabolite is 14-(R) hydroxyclarithromycin (14-OH-clarithromycin). The other metabolite, namely 14-(S) hydroxyclarithromycin is inactive. The purpose of this study was to show the hydroxylation of CLA at the 14 position to form the R and S epimers and to determine the metabolic ratio of 14ROHCLA/CLA and 14SOHCLA/CLA for understanding the metabolization. This study suggest that in healthy adults, the individual variations in therapeutic responses to clarithromycin can be assumed by taking the drug and its metabolites ratios. Clarithromycin and metabolites ratios increase during metabolization.
Asunto(s)
Antibacterianos/farmacocinética , Claritromicina/farmacocinética , Adolescente , Adulto , Antibacterianos/farmacología , Área Bajo la Curva , Biotransformación , Claritromicina/farmacología , Semivida , Humanos , Hidroxilación , Masculino , Persona de Mediana Edad , Estereoisomerismo , Adulto JovenRESUMEN
Several 5-(3,4-dichlorophenyl)-2-(aroylmethyl)thio-1,3,4-oxadiazoles were synthesized and characterized by elemental analyses, IR and nuclear magnetic resonance spectra. All compounds were evaluated for anti-inflammatory activity by determining their ability to provide protection against carregeenan-induced edema in rat paw. In addition, ulcerogenic activity was determined. The anti-inflammatory data scoring showed that compounds 5e, 5f and 5g, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5f was comparable to that of the reference drug indometacin (CAS 53-86-1).
Asunto(s)
Antiinflamatorios/síntesis química , Antiinflamatorios/farmacología , Oxadiazoles/síntesis química , Oxadiazoles/farmacología , Tionas/síntesis química , Tionas/farmacología , Animales , Antiinflamatorios/toxicidad , Carragenina , Cristalografía por Rayos X , Diseño de Fármacos , Edema/inducido químicamente , Edema/prevención & control , Pie/patología , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Masculino , Modelos Moleculares , Ratas , Ratas Sprague-Dawley , Espectrofotometría Infrarroja , Espectroscopía Infrarroja por Transformada de Fourier , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patologíaRESUMEN
Ten new 1-thiocarbamoyl-3-(phenyl and/or 4-substituted phenyl)-5-(3,4-dimethoxyphenyl and/or 2-chloro-3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole derivatives were synthesized by reacting 1,3-diphenylpropen-1-ones and thiosemicarbazide. The chemical structures of the compounds were verified by means of their IR, 1H-NMR, ESI-MS spectroscopic data and elementary analyses. All the compounds were investigated for their ability to selectively inhibit monoamine oxidase (MAO) by in-vitro tests. Monoamine oxidase was isolated and purified from the mitochondrial extracts of rat-liver homogenates and human platelets. Monoamine oxidase inhibitory activities of the compounds were compared with pargyline and clorgyline. Most of the compounds inhibited the total activity of rat liver homogenates. The monoamine oxidase-A inhibitory effects of 1-thiocarbamoyl-3-(4-methoxyphenyl)-5-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1-thiocarbamoyl-3-(4-methoxyphenyl)-5-(2-chloro-3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole were detected as potent as clorgyline. Selective and irreversible inhibition of rat liver monoamine oxidase-A by synthesized compounds have promising features for designing the new selective monoamine oxidase A inhibitors as potent and reliable anti-depressants in the future.
Asunto(s)
Inhibidores de la Monoaminooxidasa/síntesis química , Pirazoles/síntesis química , Tiocarbamatos/síntesis química , Animales , Plaquetas/enzimología , Diseño de Fármacos , Humanos , Técnicas In Vitro , Hígado/efectos de los fármacos , Hígado/enzimología , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/farmacología , Pirazoles/química , Pirazoles/farmacología , Ratas , Espectrofotometría Infrarroja , Relación Estructura-Actividad , Tiocarbamatos/química , Tiocarbamatos/farmacologíaRESUMEN
Clarithromycin is a broad-spectrum macrolide antibacterial agent which is effective both in vitro and in vivo against the major pathogens responsible for respiratory tract infections. Clarithromycin's principal metabolite is 14-(R) hydroxyclarithromycin (14-OH-clarithromycin). The other metabolite, namely 14-(S) hydroxyclarithromycin is inactive. The purpose of this study was to show the hydroxylation of CLA at the 14 position to form the R and S epimers and to determine the metabolic ratio of 14ROHCLA/CLA and 14SOHCLA/CLA for understanding the metabolization. This study suggest that in healthy adults, the individual variations in therapeutic responses to clarithromycin can be assumed by taking the drug and its metabolites ratios. Clarithromycin and metabolites ratios increase during metabolization.
Asunto(s)
Antibacterianos/metabolismo , Claritromicina/análogos & derivados , Claritromicina/metabolismo , Adolescente , Adulto , Humanos , Hidroxilación , Masculino , Persona de Mediana Edad , Estereoisomerismo , Adulto JovenRESUMEN
In this study, fifteen 2,3-disubstituted-4-thiazolidinone derivatives were synthesized by the reaction of Schiff bases and alpha-mercaptoacetic acid. The structures of the compounds were elucidated by IR, 1H-NMR, 13C-NMR, mass spectral data and elementary analysis. The antihistaminic and anticholinergic activities of the compounds were determined by tests performed on isolated guinea pig trachea in comparison with aminophylline (CAS 317-34-0). Compound 15 (3-[3-(2-methyl-piperidine-1-yl)propyl]-2-(4-methyl-phenyl)thiazolidin-4-one hydrochloride) showed the highest inhibition (53 %).
Asunto(s)
Antagonistas Colinérgicos/síntesis química , Antagonistas Colinérgicos/farmacología , Antagonistas de los Receptores Histamínicos/síntesis química , Antagonistas de los Receptores Histamínicos/farmacología , Tiazolidinas/síntesis química , Tiazolidinas/farmacología , Acetilcolina/antagonistas & inhibidores , Acetilcolina/farmacología , Animales , Femenino , Cobayas , Técnicas In Vitro , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Contracción Muscular/efectos de los fármacos , Bases de Schiff/síntesis química , Bases de Schiff/farmacología , Tráquea/efectos de los fármacos , Vasodilatadores/antagonistas & inhibidores , Vasodilatadores/farmacologíaRESUMEN
A series of 1,2,5-trisubstituted 4(1H)-pyridinone derivatives (7-14) were synthesised by using 4-pyrone derivatives with primary amines in ethanol. The structures of the synthesised compounds were confirmed by analytical and spectral data (UV, IR and 1H-NMR and microanalysis). Analgesic and antiinflammatory activities of the synthesised compounds were investigated by acetic acid-induced writhing syndrome and carrageenan rat paw edema tests. All of the test compounds exhibited higher analgesic activities than acetyl salicylic acid and showed higher antiinflammatory activities than indomethacin. The anti-inflammatory activity and gastric ulceration potential of the compounds were tested using indomethacin as reference drug.