RESUMEN
The current study aimed to investigate the pharmacokinetics of bromhexine hydrochloride in broilers after single intravenous (IV) and oral (PO) administration at 2.5 mg/kg body weight (BW). The trial adopted a randomized, parallel-controlled design, where 20 twelve-wk-old broilers were randomly assigned to either the PO or IV group. Blood samples were collected at predetermined time points, and plasma was further separated for analysis. The bromhexine hydrochloride concentrations in plasma samples were determined using an ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method. Noncompartmental analysis (NCA) using Phoenix software was conducted to analyze the concentration versus time data of bromhexine hydrochloride in every chicken. Subsequently, the main pharmacokinetic parameters between the 2 groups were statistically analyzed using SPSS software. Results from NCA revealed that after oral administration at 2.5 mg/kg BW, bromhexine hydrochloride exhibited slow absorption, reaching an average peak concentration of 32.72 ng/mL at 1.78 h. However, incomplete absorption was observed, with an absolute bioavailability of only 20.06% ± 10.84%. Additionally, bromhexine hydrochloride displayed wide distribution, with a steady-state distribution volume (VSS) of 22.55 ± 13.45 L/kg, and slow elimination, with a clearance (Cl) of 1.52 ± 0.38 L/h/kg. Furthermore, gender effects were assessed on the pharmacokinetics of bromhexine hydrochloride in broilers, revealing better absorption in male broilers compared to females. This disparity may be attributed to the faster blood flow and richer blood volume typically found in male broilers.
Asunto(s)
Bromhexina , Pollos , Animales , Masculino , Administración Oral , Femenino , Bromhexina/farmacocinética , Bromhexina/administración & dosificación , Inyecciones Intravenosas/veterinaria , Espectrometría de Masas en Tándem/veterinaria , Distribución Aleatoria , Disponibilidad Biológica , Administración Intravenosa/veterinariaRESUMEN
INTRODUCTION: Major unmet needs remain for improved antibiotic treatment in lung infections. While development of new antibiotics is needed to overcome resistance, other approaches to optimize therapy using existing agents are also attractive. Ambroxol induces lung autophagy at human-relevant doses and improves lung levels of several approved antibiotics. Areas covered: This review discusses preclinical and clinical studies of the effects of ambroxol (and its prodrug precursor bromhexine) co-treatment upon levels of antibiotics in lung tissue, sputum, and bronchoalveolar lavage fluid. Expert opinion: Ambroxol co-treatment is associated with significant increases in lung tissue and airway surface fluid levels of a range of antibiotics including beta lactams, glycopeptides, macrolides, nitrofurans, and rifamycins. In most cases, the increased levels are only modest and are insufficient to overcome high-level resistance against that same antibiotic class, and so co-treatment with ambroxol is unlikely to alter clinical outcomes. Additionally, for most antibiotics there is no evidence that outcomes in non-resistant disease are improved by higher drug levels, and there is limited efficacy of co-treatment of antibiotics with ambroxol for most pathogens. The two cases where ambroxol may improve therapy are rifampin-sensitive tuberculosis and non-tuberculous mycobacterial infection, and vancomycin sensitive methicillin resistant Staphylococcus aureus pneumonia.
Asunto(s)
Ambroxol/farmacología , Antibacterianos/farmacocinética , Bromhexina/farmacología , Ambroxol/administración & dosificación , Animales , Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Bromhexina/administración & dosificación , Farmacorresistencia Bacteriana , Expectorantes/administración & dosificación , Expectorantes/farmacología , Humanos , Pulmón/metabolismo , Enfermedades Pulmonares/tratamiento farmacológico , Distribución TisularRESUMEN
OBJECTIVE: Although association studies in the general population may be relevant for determining susceptibility to chronic obstructive pulmonary disease (COPD), they may be less applicable for pharmacogenetics research in participants who have already acquired the disease. PATIENTS AND METHODS: A genome-wide methylation profiling (generated by HumanMethylation450 BeadChips study was performed on peripheral blood mononuclear cells of 24 patients with AECOPD (acute exacerbation COPD), with good and poor responsiveness to standard corticosteroid treatment. Pyrosequencing was used to replicate the selected CpG sites in 50 patients with AECOPD with standard corticosteroid treatment. RESULTS: The results showed the patients with AECOPD with good and poor response to standard corticosteroid treatment have a distinct DNA methylation pattern. A total of 23 CpG loci located in 19 known gene regions, including gene-body and promoter, appeared to be significantly differentially methylated. Replication by pyrosequencing revealed that one CpG site in PSMD8 showed the same trend of differential methylation and reached to statistical significance as the microarray result. CONCLUSION: Our preliminary findings provide evidence for molecular heterogeneity in patients with AECOPD, which may contribute to significant differences in their response to COPD treatment.
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Corticoesteroides/administración & dosificación , Metilación de ADN/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Corticoesteroides/efectos adversos , Anciano , Albuterol/administración & dosificación , Albuterol/efectos adversos , Bromhexina/administración & dosificación , Bromhexina/efectos adversos , Bromhexina/sangre , Islas de CpG/genética , Femenino , Genoma Humano/efectos de los fármacos , Genoma Humano/genética , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Masculino , Persona de Mediana Edad , Prednisolona/administración & dosificación , Prednisolona/efectos adversos , Regiones Promotoras Genéticas/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
The objective of the present study was to evaluate the effectiveness ascoril therapy in comparison with the treatment using the mucoactive agent lasolvan in the adult patients suffering from productive cough associated with acute viral respiratory infection. Patients and methods. The study included 120 patients suffering from productive cough associated with acute viral respiratory infection. They were divided into two groups. The patients comprising group 1 (n=6.) were treated with ascoril, those in group 2 (n=60) were given lasolvan. Results. The effectiveness of the treatment of cough in group 1 was found to be higher compared with that in group 2 (p<0.05); moreover, it was associated with better dynamics of certain indicators of the quality of life, such as the social activity level, vitality, and general health (p<0.05). The safety of the proposed treatment was confirmed by the absence of the adverse events throughout the entire treatment period.
Asunto(s)
Albuterol/farmacología , Ambroxol/farmacología , Bromhexina/farmacología , Broncodilatadores/farmacología , Tos/tratamiento farmacológico , Expectorantes/farmacología , Guaifenesina/farmacología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Enfermedad Aguda , Adulto , Albuterol/administración & dosificación , Ambroxol/administración & dosificación , Bromhexina/administración & dosificación , Broncodilatadores/administración & dosificación , Tos/etiología , Tos/virología , Combinación de Medicamentos , Expectorantes/administración & dosificación , Femenino , Guaifenesina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/virología , Resultado del TratamientoRESUMEN
This paper reports results of international multicentre non-interventional clinical study of the effectiveness and safety of ascoril expectorant for the treatment of cough in Kazakhstan and Uzbekistan. The study included 16312 patients examined in different cities during 2011-2012. It showed that ascoril expectorant (Glenmark) at a standard dose is an effective agent for the treatment of cough in children above 3 years and adults aged up to 78 years with ARVI and acute bronchitis, exacerbation of these conditions or grade I-II chronic obstructire pulmonary disease. Most patients reported good therapeutic effect within 1 day after intake. Ascoril expectorant caused no adverse reactions and was well tolerated by the patients. 91% of the attending physicians describe the drug as highly effective.
Asunto(s)
Albuterol , Bromhexina , Tos , Guaifenesina , Infecciones del Sistema Respiratorio/complicaciones , Adolescente , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/efectos adversos , Adulto , Anciano , Albuterol/administración & dosificación , Albuterol/efectos adversos , Bromhexina/administración & dosificación , Bromhexina/efectos adversos , Preescolar , Tos/tratamiento farmacológico , Tos/etiología , Tos/fisiopatología , Combinación de Medicamentos , Monitoreo de Drogas , Expectorantes/administración & dosificación , Expectorantes/efectos adversos , Femenino , Guaifenesina/administración & dosificación , Guaifenesina/efectos adversos , Humanos , Kazajstán , Masculino , Pacientes Ambulatorios , Gravedad del Paciente , Infecciones del Sistema Respiratorio/clasificación , Infecciones del Sistema Respiratorio/fisiopatología , Resultado del Tratamiento , UzbekistánRESUMEN
(E)-4-hydroxydemethylbromhexine (E-4-HDMB) and (E)-3-hydroxydemethylbromhexine (E-3-HDMB) were found as major metabolites, while (Z)-4-hydroxydemethylbromhexine and (Z)-3-hydroxydemethylbromhexine as minor metabolites of bromhexine in human plasma. These compounds were identified in comparison with synthetic authentic samples. A sensitive and selective rapid resolution liquid chromatography tandem mass spectrometry (RRLC-MS/MS) method was developed to quantify the concentration of bromhexine and its two major metabolites (E-4-HDMB and E-3-HDMB) in human plasma. Following solid phase extraction, the analytes were separated on a Zorbax 1.8microm particle size reversed-phase C(18) column, using a gradient elution program with solvents consisting of 0.1% formic acid in acetonitrile and 0.1% formic acid in 5mM ammonium acetate at a flow rate of 0.7mL/min. Detection was carried out with an Agilent 6460 triple-quadrupole mass spectrometer operated with an electrospray ionization source mode operated in the positive ion mode. The recovery of bromhexine, E-4-HDMB, E-3-HDMB, and internal standard (IS) was 63.1-70.9%, 60.5-68.4%, 57.0-63.5%, and 87.8%, respectively. The matrix factors of bromhexine, E-4-HDMB, E-3-HDMB, and IS were 89.9-96.7%, 89.6-94.8%, 90.4-91.4%, and 103%, respectively. After an oral administration of 8.0mg bromhexine to five healthy male subjects, AUC(0-24h) values of bromhexine, E-4-HDMB, and E-3-HDMB were found to be 93.5+/-31.9, 34.0+/-14.5, and 15.8+/-6.89ngh/mL, respectively; while C(max) values were 24.6+/-5.16, 3.11+/-1.13, and 5.36+/-2.55ng/mL, respectively. Plasma concentration of bromhexine, E-4-HDMB, and E-3-HDMB declined with t(1/2) which gave 3.6+/-0.5, 8.4+/-2.7, and 6.4+/-2.5h, respectively.
Asunto(s)
Bromhexina/farmacocinética , Cromatografía Liquida , Expectorantes/farmacocinética , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem , Administración Oral , Biotransformación , Bromhexina/administración & dosificación , Bromhexina/sangre , Cromatografía Liquida/normas , Remoción de Radical Alquila , Estabilidad de Medicamentos , Expectorantes/administración & dosificación , Semivida , Humanos , Hidroxilación , Masculino , Estándares de Referencia , Reproducibilidad de los Resultados , Espectrometría de Masa por Ionización de Electrospray/normas , Espectrometría de Masas en Tándem/normas , Adulto JovenRESUMEN
A simple, sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry method was developed for the quantitative determination of bromhexine in human plasma. Sample preparation involved simple liquid-liquid extraction. Simvastatin was used as internal standard. The separation of the analyte, internal standard and possible endogenous compounds were accomplished on a Shim-pack ODS column (150 mm x 4.6 mm i.d., 5 microm) with methanol-water (98:2, v/v) as mobile phase. Detection was performed in positive selected ion monitoring (SIM) mode at m/z 264.1 (for bromhexine) and m/z 441.7 (for IS). The method was validated over the range of 0.5-60 ng/mL and the results were acceptable. The method could offer the advantages of shorter run time (5.5 min) and lower LLOQ (0.5 ng/mL) with a decreased plasma volume requirement (250 microL) and it had been successfully applied to a bioequivalence study in healthy Chinese volunteers after single oral administration of 16 mg bromhexine.
Asunto(s)
Bromhexina/farmacocinética , Cromatografía Liquida/métodos , Expectorantes/farmacocinética , Espectrometría de Masa por Ionización de Electrospray/métodos , Administración Oral , Área Bajo la Curva , Bromhexina/administración & dosificación , Bromhexina/sangre , Calibración , Estudios Cruzados , Estabilidad de Medicamentos , Expectorantes/administración & dosificación , Congelación , Semivida , Humanos , Masculino , Tasa de Depuración Metabólica , Control de Calidad , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Comprimidos , Equivalencia TerapéuticaRESUMEN
Chronic pancreatitis is a progressive inflammatory condition characterized by repeated attacks of abdominal pain, and the destruction and fibrosis of the pancreatic parenchyma which causes to reduced exocrine and endocrine functions. Alcohol is the most common cause of chronic pancreatitis. Although abstinence is usually considered a prerequisite for successful treatment of alcoholic chronic pancreatitis, we often encounter patients who have repeated attacks from the compensated stage through the transitional stage. In alcoholic chronic pancreatitis, continued alcohol consumption causes changes in the digestive hormones and vagal nerve function that induce the pancreatic acinar cells to oversecrete protein, increasing the protein concentration and viscosity of the pancreatic juice. This induces protein sedimentation from the pancreatic juice and formation of protein plugs within the pancreatic duct, triggering repeated attacks of acute pancreatitis. The treatment of alcoholic chronic pancreatitis includes alleviation of symptoms, particularly abdominal pain, elimination of trigger factors, prevention of recurrence and disease progression, adjuvant therapies for pancreatic exocrine and endocrine failure. Recently, the main constituent proteins in these protein plugs have been identified, enabling trials of several therapies, such as the administration of secretin formulations and endoscopic removal. Bromhexine hydrochloride, a bronchial mucolytic, has an affinity for the pancreatic acinar cells, inducing them to secrete pancreatic juice of low viscosity. In this review, we summarize the most recent thoughts about alcoholic chronic pancreatitis, and the new treatments, and in particular, we present our findings concerning the efficacy of bromhexine hydrochloride in the treatment of this disease.
Asunto(s)
Pancreatitis Alcohólica/terapia , Alcoholismo/fisiopatología , Alcoholismo/rehabilitación , Bromhexina/administración & dosificación , Terapia Combinada , Progresión de la Enfermedad , Endoscopía , Insuficiencia Pancreática Exocrina/fisiopatología , Insuficiencia Pancreática Exocrina/terapia , Hormonas Gastrointestinales/fisiología , Humanos , Estilo de Vida , Jugo Pancreático/fisiología , Pancreatitis Alcohólica/fisiopatología , Recurrencia , Secretina/administración & dosificación , Nervio Vago/fisiopatología , ViscosidadRESUMEN
For the treatment of sicca symptoms as a manifestation of Sjögren's syndrome there are various tear substitutes as well as artificial saliva. The appropriate substances are discussed in this article. In addition to reducing symptoms, some of the effective compounds offer the advantage of infection prophylaxis in the form of better lubrication of the mucous membranes in the airways as well as reduced susceptibility to candidiasis. The presence of bromhexin in the catalogue of the statutory medical insurance agencies is recommended. Certain of the available drugs are still only available in foreign pharmacies.
Asunto(s)
Síndromes de Ojo Seco/terapia , Síndrome de Sjögren/terapia , Xerostomía/terapia , Bromhexina/administración & dosificación , Ciclosporina/administración & dosificación , Terapia por Estimulación Eléctrica , Expectorantes/uso terapéutico , Humanos , Antagonistas Muscarínicos/administración & dosificación , Soluciones Oftálmicas/administración & dosificación , Pilocarpina/administración & dosificación , Quinuclidinas/administración & dosificación , Tiofenos/administración & dosificaciónRESUMEN
Neutrophils are major culprits for the protease/antiprotease imbalance during various lung diseases, that is, chronic obstructive pulmonary disease, cystic fibrosis, idiopathic pulmonary fibrosis and adult respiratory distress syndrome. Thus, these cells are presently considered an ideal target for the pharmacologic control of tissue injury during these diseases. This study was planned in order to investigate if ambroxol and its precursor bromhexine are actually capable of preventing alpha-1-antitrypsin (A1AT) inactivation by stimulated neutrophils and possibly to look into the mechanisms underlying this event. Ambroxol inhibited the production of superoxide anion by activated neutrophils, whereas bromhexine had no inhibitory effect. Ambroxol decreased the production of hypochlorous acid (HOCl) from activated neutrophils with high efficiency, whereas bromhexine had a modest activity. Ambroxol and bromhexine were capable of limiting the chlorination of monochlorodimedon by HOCl, displaying the capacity of directly scavenging the oxidant. Ambroxol decreased the release of elastase and myeloperoxidase from activated neutrophils, whereas bromhexine was ineffective. Ambroxol prevented the A1AT inactivation by neutrophils, whereas bromhexine was completely ineffective. Among drugs currently available for in vivo use in humans, ambroxol is unique by virtue of its ability to prevent neutrophil-mediated A1AT inactivation via inhibition of HOCl production as well as HOCl scavenging. Also taking into account its capacity for curbing elastase release, the drug displays the potential to lessen the burden of oxidants/proteases and to increase the antiprotease shield at the site of inflammation. Thus, ambroxol appears to be a good candidate for raising attempts to develop new therapeutic histoprotective approaches to inflammatory bronchopulmonary diseases.
Asunto(s)
Ambroxol/farmacología , Activación Neutrófila/efectos de los fármacos , Bromhexina/administración & dosificación , Cloruros , Ciclohexanonas/antagonistas & inhibidores , Ciclohexanonas/metabolismo , Citocalasinas/farmacología , Gránulos Citoplasmáticos/efectos de los fármacos , Gránulos Citoplasmáticos/fisiología , Relación Dosis-Respuesta a Droga , Exocitosis/efectos de los fármacos , Exocitosis/fisiología , Humanos , Peróxido de Hidrógeno/metabolismo , Ácido Hipocloroso/antagonistas & inhibidores , Ácido Hipocloroso/metabolismo , Elastasa de Leucocito/antagonistas & inhibidores , Elastasa de Leucocito/metabolismo , Activación Neutrófila/fisiología , Peroxidasa/antagonistas & inhibidores , Peroxidasa/metabolismo , Especies Reactivas de Oxígeno/efectos adversos , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Superóxidos/antagonistas & inhibidores , Superóxidos/metabolismo , alfa 1-Antitripsina/metabolismo , alfa 1-Antitripsina/fisiologíaRESUMEN
The present study was undertaken to study the comparative safety and efficacy of two cough formulas viz, Ascoril expectorant and other cough formula in the management of cough associated with respiratory disorders. Fifty patients having cough associated with various respiratory disorders like bronchitis and upper or lower respiratory tract infections were randomly divided into 2 equal groups and were treated with one of the two cough formulas viz, Ascoril cough formula and other cough formula in double-blind manner over a period of 15 days. The evaluation of improvement was carried out by a rating scale using three clinical parameters--cough, sputum and breathlessness. The physicians were asked to rate the effectiveness of the therapy and patients were asked to rate the acceptability of therapy using pre-defined operational criteria. It was observed that the improvement and symptom relief was almost immediate, quicker and better in the group receiving Ascoril as compared to other group. On effectiveness parameter, 96% of the physicians rated Ascoril as having either 'very high effectiveness or high effectiveness' as opposed to only 34% of the physicians who rated other cough formula as having 'high' or 'very high effectiveness'. While on parameter of acceptability, 96% of the patients rated acceptability of Ascoril as 'high' or 'good' as opposed to only 24% of the patients who rated other cough formula 'high' or 'good'. The findings of this study suggests that Ascoril cough formula has better efficacy as well as better patient acceptability. Thus, Ascoril cough formula is superior to other cough formula in management of cough associated with respiratory disorders.
Asunto(s)
Albuterol/administración & dosificación , Bromhexina/administración & dosificación , Tos/tratamiento farmacológico , Expectorantes/administración & dosificación , Guaifenesina/administración & dosificación , Adolescente , Adulto , Albuterol/efectos adversos , Cloruro de Amonio/administración & dosificación , Cloruro de Amonio/efectos adversos , Bromhexina/efectos adversos , Niño , Preescolar , Citratos/administración & dosificación , Citratos/efectos adversos , Tos/etiología , Difenhidramina/administración & dosificación , Difenhidramina/efectos adversos , Método Doble Ciego , Combinación de Medicamentos , Expectorantes/efectos adversos , Femenino , Guaifenesina/efectos adversos , Humanos , Masculino , Estudios Prospectivos , Citrato de Sodio , Resultado del TratamientoRESUMEN
AIM: Assessment of efficacy of combined treatment of chronic bronchitis (CB) in subjects exposed to radiation after the Chernobyl accident including nonpharmacological (NP) modalities vs conventional chemotherapy (CT). MATERIALS AND METHODS: 149 patients with different forms of CB in exacerbation were divided into 2 groups. The study group of 62 patients received NP + CT. Control group of 87 patients received CT alone. The response was judged by achievement of partial or complete remission, general condition score, external respiration function. RESULTS: The combined treatment significantly more frequently (p < 0.05) led to CB remission, more marked improvement of the patient's condition. External respiration improved insignificantly. CONCLUSION: NP in combined treatment of CB exacerbation improved the treatment results.
Asunto(s)
Bronquitis/etiología , Centrales Eléctricas , Traumatismos por Radiación/etiología , Liberación de Radiactividad Peligrosa , Adolescente , Corticoesteroides/administración & dosificación , Adulto , Aminofilina/administración & dosificación , Bromhexina/administración & dosificación , Bronquitis/tratamiento farmacológico , Bronquitis/terapia , Broncodilatadores/administración & dosificación , Enfermedad Crónica , Terapia Combinada , Difenhidramina/administración & dosificación , Quimioterapia Combinada , Campos Electromagnéticos , Expectorantes/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Humanos , Terapia por Láser , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/radioterapia , Traumatismos por Radiación/terapia , Factores de Tiempo , UcraniaRESUMEN
The purpose of the present clinical studies was to determine the clinical efficacy of a combined parenteral and oral treatment with Bisolvon in combination with antibiotics in bovines suffering from acute respiratory disease. To this end four trials were conducted in respiratory diseased bovines; a total of 619 animals were evaluated. The animals were randomly assigned to one of two treatment groups within each study and were treated either with enrofloxacin, cefquinome, ceftiofur or florfenicol. The Bisolvon group was additionally treated with Bisolvon over 5 consecutive days. Daily clinical examinations were carried out over a period of 6 days. The clinical respiratory score, the primary parameter, representing a summation of the scoring points for the parameters respiratory rate, nasal discharge, spontaneous coughing, lung sounds and grade of dyspnoea and the clinical index score, which additionally included the general parameters fever, demeanour and feed intake, were significantly lower in the Bisolvon groups compared to the controls at all examinations after initiation of therapy in all trials with the exception of day 2 in one study. Lower values correspond to a less severe clinical condition. This consistent result as well as the evaluation of the single parameters are indicative of an acceleration of the recovery of the animals additionally treated with Bisolvon.
Asunto(s)
Antiinfecciosos/uso terapéutico , Bromhexina/uso terapéutico , Enfermedades de los Bovinos/tratamiento farmacológico , Cefalosporinas/uso terapéutico , Quimioterapia Combinada/uso terapéutico , Fluoroquinolonas , Quinolonas/uso terapéutico , Infecciones del Sistema Respiratorio/veterinaria , Tianfenicol/análogos & derivados , Enfermedad Aguda , Administración Oral , Animales , Antiinfecciosos/administración & dosificación , Bromhexina/administración & dosificación , Bovinos , Cefalosporinas/administración & dosificación , Quimioterapia Combinada/administración & dosificación , Enrofloxacina , Inyecciones , Quinolonas/administración & dosificación , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Tianfenicol/administración & dosificación , Tianfenicol/uso terapéuticoRESUMEN
The purpose of the present study was to determine whether bromhexine (Solvex) affects the rate of tear secretion or the concentration of lysosyme in the tear fluid in healthy subjects. The rate of tear secretion and lysosyme concentration in tear fluid were estimated in 56 healthy volunteers before and after 3 weeks of oral administration of placebo (tablets of vitamin C, 200 mg per day) followed by bromhexine tablets, 32 mg per day. Shirmer's test I was performed to evaluate the tear secretion, and the lysosyme plate method was used to detect lysosyme concentration. Shirmer's test showed similar results before and after placebo and bromhexine administration. In conclusion, oral bromhexine was found to have no effect on the rate of tear secretion, nor on the concentration of lysosyme in the tear fluid of healthy subjects.
Asunto(s)
Bromhexina/administración & dosificación , Expectorantes/administración & dosificación , Proteínas del Ojo/metabolismo , Muramidasa/metabolismo , Lágrimas/metabolismo , Administración Oral , Adulto , Anciano , Humanos , Aparato Lagrimal/efectos de los fármacos , Aparato Lagrimal/metabolismo , Persona de Mediana EdadRESUMEN
The potentiality of interaction of bromhexine (1) with beta-cyclodextrin was investigated by spectrophotometric methods. Differential UV spectrophotometry revealed a decrease in the optical density of the drug in presence of beta-cyclodextrin (beta-CD) and a hypsochromic shift in one of the two wavelengths of maximum absorption of the drug from 312 to 309 nm in presence of beta-CD. The continuous variation method based on spectrophotometric measurements revealed the formation of 1:1 complex between the drug and beta-CD. The solubility of 1 in presence of beta-CD was found to increase to a marked extent. Also the dissolution profiles of the drug, physical mixture of the drug and beta-CD as well as the prepared complex showed a great enhancement of the dissolution properties of 1 in presence of beta-CD either in a physical mixture or in complexed state. The partition coefficient between n-octanol and phosphate buffer of pH 7.4 of 1 and its beta-CD complex was also determined. Investigation of the transdermal diffusion of the drug and the complex in different dermatological vehicles was carried out using abdominal rat skin. A linear relationship was found to exist between the amount of drug released and the square root of the time. The drug showed the highest release characteristics from methyl cellulose > PVP > PEG 400, also inclusion complexation of 1 in beta-CD causes an improvement in the release properties of the drug from the investigated dermatological vehicles.
Asunto(s)
Bromhexina/administración & dosificación , Bromhexina/farmacocinética , Ciclodextrinas/química , Administración Cutánea , Animales , Bromhexina/química , Difusión , Masculino , Vehículos Farmacéuticos , Ratas , Solubilidad , Espectrofotometría UltravioletaAsunto(s)
Síndromes de Ojo Seco/tratamiento farmacológico , Aparato Lagrimal/metabolismo , Receptores sigma/aislamiento & purificación , Administración Tópica , Animales , Bromhexina/administración & dosificación , Bromhexina/análogos & derivados , Bromhexina/farmacología , Carbacol/farmacología , Relación Dosis-Respuesta a Droga , Proteínas del Ojo/metabolismo , Femenino , Aparato Lagrimal/citología , Aparato Lagrimal/efectos de los fármacos , Masculino , Soluciones Oftálmicas , Conejos , Lágrimas/metabolismoAsunto(s)
Tasa de Secreción/efectos de los fármacos , Lágrimas/metabolismo , Bromhexina/administración & dosificación , Bromhexina/farmacología , Síndromes de Ojo Seco/tratamiento farmacológico , Eledoisina/administración & dosificación , Eledoisina/farmacología , Fluorofotometría , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Humanos , Aparato Lagrimal/efectos de los fármacos , Aparato Lagrimal/metabolismo , Soluciones Oftálmicas , Oximetazolina/administración & dosificación , Oximetazolina/farmacología , Timolol/administración & dosificación , Timolol/farmacologíaRESUMEN
The mucolytic activity of azelastine, an antiallergic/antiasthmatic drug, in mice and rats was investigated. The oral administration of test compounds 30 min before phenol red i.p. injection stimulated dye secretion in the trachea of mice. The resulting oral ED50's (mg/kg) were: azelastine, 0.16; salbutamol, 2.5; N-acetylcysteine, 61.8; S-Carboxymethyl-l-cysteine, < 100; bromhexine, > 100; and potassium iodide, approximately 200. In rats, several drugs stimulated secretion of fluorescein sodium (FINa) in the tracheobronchial lumen. The resulting oral ED50's (mg/kg) were: azelastine, 0.33; terbutaline, 0.3; salbutamol, 0.89; and S-carboxymethyl-l-cysteine, 56.8. Terfenadine and diphenhydramine (1-10 mg/kg, p.o.) did not stimulate tracheal secretion in rats and mice. The mucolytic activity of azelastine may contribute to its overall effectiveness, including antitussive activity in asthmatics. Finally, this activity seems to be dissociated from its H1-histamine receptor blocking activity.
Asunto(s)
Expectorantes/farmacología , Antagonistas de los Receptores Histamínicos H1/farmacología , Ftalazinas/farmacología , Tráquea/efectos de los fármacos , Acetilcisteína/administración & dosificación , Acetilcisteína/farmacología , Administración Oral , Albuterol/administración & dosificación , Albuterol/farmacología , Animales , Bromhexina/administración & dosificación , Bromhexina/farmacología , Carbocisteína/administración & dosificación , Carbocisteína/farmacología , Difenhidramina/administración & dosificación , Difenhidramina/farmacología , Fluoresceína , Fluoresceínas/metabolismo , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Masculino , Ratones , Fenolsulfonftaleína/metabolismo , Ftalazinas/administración & dosificación , Yoduro de Potasio/administración & dosificación , Yoduro de Potasio/farmacología , Ratas , Terbutalina/administración & dosificación , Terbutalina/farmacología , Tráquea/metabolismoRESUMEN
We studied the ultrastructural changes of the corneal epithelium of the experimental rabbit dry eye and the effects of three topically applied eye-drops. Fourty rabbits were divided into experimental rabbit dry eye group, 0.1% bromhexine-treated group, 50% Chinese medicinal herb-treated group and 0.01% retinoic acid-treated group. Ten days after surgical removal of lacrimal gland, nictitating membrane and Harder's gland of the rabbit eyes, and corroding the conjunctiva with 50% trichloroacetic acid, the rabbit eyes showed typical dry eye signs. A lot of pathologic ultrastructural changes of the corneal epithelium were observed. Fourteen days after topically applying the three eye-drops, no significant effect was found on the ultrastructural changes of the dry eye corneal epithelium in the 0.1% bromhexine-treated and 50% Chinese medicinal herb-treated groups. However, in the 0.01% retinoic acid-treated eyes, normal microvilli and microplicae reappeared, denuded corneal epithelium was covered by new epithelial cells, no cell swelled, degenerated mitochondria recovered, basement membrane returned completely, and the completely recovered corneal epithelial cell count showed a significant difference compared with the control (P < 0.01). We conclude that removing the lacrimal gland, nictitating membrane and Harder's gland of rabbit eye, and corroding the conjunctiva with 50% trichloroacetic acid can result in rabbit dry eye and topically applying 0.01% retinoic acid can promote the recovery of the dry corneal epithelium.
Asunto(s)
Bromhexina/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Síndromes de Ojo Seco/tratamiento farmacológico , Tretinoina/administración & dosificación , Animales , Córnea/ultraestructura , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/patología , Epitelio/ultraestructura , Aparato Lagrimal/cirugía , Microscopía Electrónica , Soluciones Oftálmicas , ConejosRESUMEN
The effect of Paxirasol nasal spray has been examined in 25 patients by the open method. The goal of the study was to assess and evaluate the clinical effectivity of the product and to observe the eventual side-effects. Among the examined patients 14 were acute and 11 chronic disease cases. In 20 of the 25 patients treated with Paxirasol nasal spray the pathological alteration of the nasal mucosa was controlled, mild alteration persisted in 4 patients, and moderately severe condition in 1 patient. The product significantly improved the viscosity of nasal discharge in all of them. The cessation or moderation of difficult nose blowing improved the general condition of the patients and accelerated recovery. Occasionally manifesting olfactory disorders ceased as well. The treatment needed not be discontinued because of the development of side-effects. Considering the healing tendency difference could be observed between the acute and chronic cases, especially in rhinitis sicca patients who were treated with Paxirasol nasal spray. In 23 of the 25 patients notable improvement of both the subjective and objective symptoms was observed. Paxirasol nasal spray is of value in very frequently occurring diseases of the nasal mucosa accompanied by dehydration. In the majority of acute disease patients the use of the product as monotherapy may result in complete cessation of symptoms.