RESUMO
Chemotherapy induced nausea and vomiting (CINV) and post-operative nausea and vomiting (PONV) is a problem, often occurs in patient. Inspite of high bioavailability, the demerits such as: hepatic first pass metabolism and invasive nature of oral and parenteral dosage forms can be avoided with anti-emetic therapy of transdermal device. The major objective of the present study is to modify the hydrochloride (HCl) form of Ondansetron (OND) to the base form followed by improvement of solubility and permeability of OND by employing solid dispersion (SD) loaded patches. Preformulation study, as observed, begins with an approach to enthuse solubility of OND by SD technique choosing different carriers. The choice of carriers was rationalized by phase solubility study. Several combinations of transdermal films were prepared with pure drug, carriers and SDs with plasticizer Ka values of OND-HPßCD binary system were found lower (54.43 to 187.57 M-1) than that of OND-PVP K-30 binary system (1156.77 to 12203.6 M-1). The drug content of SDs and patches were found satisfactory. Better permeation rate (236.48±3.66 µg/3.935 cm2) with promising flux enhancement (8.30 fold) was found with DBP loaded SD patch (P6*). Hence, enhancement of solubility and permeability of P6* ensures that it can successfully enhance the bioavailability
Assuntos
Plastificantes/efeitos adversos , Solubilidade , Ondansetron/antagonistas & inibidores , Pacientes/classificação , Vômito , Preparações Farmacêuticas/análise , Náusea e Vômito Pós-Operatórios , Formas de Dosagem , Tratamento Farmacológico/instrumentação , Métodos , Filmes Cinematográficos/classificaçãoRESUMO
Bisphenol A [2,2-bis(4-hydroxyphenyl)propane] (BPA), 4-nonylphenol (NP) and di(2-ethylhexyl)phthalate (DEHP), and its metabolite mono-2-ethylhexyl phthalate (MEHP) are chemicals found in plastics, which act as endocrine disruptors (EDs) in animals, including human. EDs act like hormones in the endocrine system, and disrupt the physiologic function of endogenous hormones. Most people are exposed to different endocrine disruptors and concern has been raised about their true effect on reproductive organs. In the testis, they seem to preferentially attack developing testis during puberty rather than adult organs. However, the lack of information about the molecular mechanism, and the apparently controversial effect observed in different models has hampered the understanding of their effects on mammalian spermatogenesis. In this review, we critically discuss the available information regarding the effect of BPA, NP and DEHP/ MEHP upon mammalian spermatogenesis, a major target of EDs. Germ cell sloughing, disruption of the blood-testis-barrier and germ cell apoptosis are the most common effects reported in the available literature. We propose a model at the molecular level to explain the effects at the cellular level, mainly focused on germ cell apoptosis.
Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Ocupacionais do Ar/toxicidade , Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/toxicidade , Infertilidade Masculina/induzido quimicamente , Fenóis/efeitos adversos , Fenóis/toxicidade , Plastificantes/toxicidade , Espermatogênese/efeitos dos fármacos , Animais , Apoptose/fisiologia , Células Germinativas/efeitos dos fármacos , Humanos , Masculino , Plastificantes/efeitos adversos , Plastificantes/química , Espermatogênese/fisiologia , Testículo/efeitos dos fármacosRESUMO
Bisphenol A [2,2-bis(4-hydroxyphenyl)propane] (BPA), 4-nonylphenol (NP) and di(2-ethylhexyl)phthalate (DEHP), and its metabolite mono-2-ethylhexyl phthalate (MEHP) are chemicals found in plastics, which act as endocrine disruptors (EDs) in animals, including human. EDs act like hormones in the endocrine system, and disrupt the physiologic function of endogenous hormones. Most people are exposed to different endocrine disruptors and concern has been raised about their true effect on reproductive organs. In the testis, they seem to preferentially attack developing testis during puberty rather than adult organs. However, the lack of information about the molecular mechanism, and the apparently controversial effect observed in different models has hampered the understanding of their effects on mammalian spermatogenesis. In this review, we critically discuss the available information regarding the effect of BPA, NP and DEHP/ MEHP upon mammalian spermatogenesis, a major target of EDs. Germ cell sloughing, disruption of the blood-testis-barrier and germ cell apoptosis are the most common effects reported in the available literature. We propose a model at the molecular level to explain the effects at the cellular level, mainly focused on germ cell apoptosis.
Assuntos
Animais , Humanos , Masculino , Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Ocupacionais do Ar/toxicidade , Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/toxicidade , Infertilidade Masculina/induzido quimicamente , Fenóis/efeitos adversos , Fenóis/toxicidade , Plastificantes/toxicidade , Espermatogênese/efeitos dos fármacos , Apoptose/fisiologia , Células Germinativas/efeitos dos fármacos , Plastificantes/efeitos adversos , Plastificantes/química , Espermatogênese/fisiologia , Testículo/efeitos dos fármacosRESUMO
The effects of chronic intake of di(2-ethylhexyl)phthalate (DEHP) on the main intermediate glycolytic metabolites in liver and gastrocnemius muscle were investigated in experimental animals. Male Wistar rats (90-100 g) were fed for 21 days either with a standard chow or the same diet supplemented with 2% (w/w) of DEHP. The DEHP-fed rats had an altered in vivo glucose tolerance associated with abnormal glucose intermediate metabolite contents in liver and skeletal muscle. In these rats, the hepatic content of glucose-6-phosphate (G-6-P), fructose-6-phosphate, pyruvate, lactate, glucose-1-phosphate and glycogen decreased. At the same time, the G-6-P content decreased while the pyruvate and lactate levels increased in skeletal muscle. These data, along with the high plasma glucose concentration and the normal lactate blood levels of this group, could indicate that DEHP-fed rats could present a deficiency in muscle glucose and lactate transport, a reduction of the flux through muscle hexokinase and hepatic glucokinase, and a reduction in glycogen synth-
Assuntos
Glicemia/metabolismo , Dietilexilftalato/administração & dosagem , Glicólise/efeitos dos fármacos , Fígado/efeitos dos fármacos , Plastificantes/administração & dosagem , Ração Animal , Animais , Dietilexilftalato/efeitos adversos , Contaminação de Alimentos , Glicólise/fisiologia , Ácido Láctico/sangue , Ácido Láctico/metabolismo , Fígado/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Plastificantes/efeitos adversos , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
Premature breast development (thelarche) is the growth of mammary tissue in girls younger than 8 years of age without other manifestations of puberty. Puerto Rico has the highest known incidence of premature thelarche ever reported. In the last two decades since this serious public health anomaly has been observed, no explanation for this phenomenon has been found. Some organic pollutants, including pesticides and some plasticizers, can disrupt normal sexual development in wildlife, and many of these have been widely used in Puerto Rico. This investigation was designed to identify pollutants in the serum of Puerto Rican girls with premature thelarche. A method for blood serum analysis was optimized and validated using pesticides and phthalate esters as model compounds of endocrine-disrupting chemicals. Recovery was > 80% for all compounds. We performed final detection by gas chromatography/mass spectrometry. We analyzed 41 serum samples from thelarche patients and 35 control samples. No pesticides or their metabolite residues were detected in the serum of the study or control subjects. Significantly high levels of phthalates [dimethyl, diethyl, dibutyl, and di-(2-ethylhexyl)] and its major metabolite mono-(2-ethylhexyl) phthalate were identified in 28 (68%) samples from thelarche patients. Of the control samples analyzed, only one showed significant levels of di-isooctyl phthalate. The phthalates that we identified have been classified as endocrine disruptors. This study suggests a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population.
Assuntos
Mama/crescimento & desenvolvimento , Ácidos Ftálicos/efeitos adversos , Plastificantes/efeitos adversos , Puberdade Precoce/induzido quimicamente , Estudos de Casos e Controles , Criança , Pré-Escolar , Sistema Endócrino/efeitos dos fármacos , Exposição Ambiental , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Lactente , Ácidos Ftálicos/sangue , Puberdade Precoce/epidemiologia , Saúde Pública , Porto Rico/epidemiologiaRESUMO
O estudo do comportamento térmico é indispensável para a caracterização e definição das propriedades de materiais poliméricos, pois a escolha de um determinado tipo de polímero muitas vezes está relacionado com a sua estabilidade térmica. No campo farmacêutico o processo de revestimento de formas sólidas é realizado empregando filmes poliméricos. Neste particular, poucas são as informações relatadas na literatura envolvendo processo de síntese e estudos do comportamento térmico dessa classe de materiais. Em vista disso, buscou-se avaliar em filmes farmacêuticos: o efeito do uso de concentrações variadas e crescentes de plastificante, o grau de interação entre o plastificante e o polímero e o comportamento térmico dos materiais de partida e produtos finais...
Assuntos
Plastificantes/efeitos adversos , Polímeros , Comprimidos com Revestimento Entérico , Tecnologia Farmacêutica , Análise Espectral/métodos , Calorimetria , TermogravimetriaRESUMO
Phthalate esters are a large group of chemical compounds used in the production of plastics, household articles, packages, cosmetics and plant pesticides. World production of phthalates is estimated to be several million tons a year. Recent observations indicate some mutagenic, cancerogenic and orchidotoxic effect of these compounds. Therefore, to assess the extent of risk it is imperative to have an adequate analytical method. The following is simple and relatively inexpensive. The study group consisted of 58 men.