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1.
Biol Pharm Bull ; 43(12): 1954-1959, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33268715

RESUMO

The taste of medicines can significantly affect patient adherence. Pediatric patients often cannot take powder medicines because of their unpleasant taste. Therefore, patients' parents and health care professionals, including pharmacists, often combine medicines with food or beverages to make them easier for pediatric patients to consume because this can reduce their unpleasant taste. The purpose of this study was to evaluate the palatability of powder formulations of azithromycin and carbocysteine and explore their combination with food or beverages to improve palatability for pediatric patients. We quantitatively evaluated the palatability of powder formulations by performing the gustatory sensation test using the visual analog scale score. The gustatory sensation tests were performed on 16 healthy adult volunteers (age 23.0 ± 2.6 years) and indicated that some food and beverages improved the palatability of the powder formulations of azithromycin and carbocysteine. The results of this study indicate that ice cream improves the palatability of azithromycin, while yogurt improves the palatability of carbocysteine. Moreover, the subjects recommended these same combinations for pediatric patients. This study suggests that some foods and beverages improve the palatability of powder formulations, thereby decreasing the possibility that pediatric patients will refuse medications because of their unpleasant taste.


Assuntos
Bebidas , Composição de Medicamentos/métodos , Alimentos , Pós/administração & dosagem , Pós/síntese química , Paladar/efeitos dos fármacos , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/síntese química , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/síntese química , Azitromicina/administração & dosagem , Azitromicina/síntese química , Carbocisteína/administração & dosagem , Carbocisteína/síntese química , Estudos Cross-Over , Feminino , Humanos , Masculino , Paladar/fisiologia , Adulto Jovem
2.
Respir Med ; 175: 106190, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33217537

RESUMO

BACKGROUND: International guidelines recommend mucolytic agents as add-on therapy in selected patients with COPD because they may reduce exacerbations and improve health status. As the evidence varies among mucolytic agents, we used the Delphi method to assess consensus amongst an international panel of COPD experts on mucolytics use in COPD. METHODS: 53 COPD experts from 12 countries were asked to complete an online questionnaire and rate their agreement with 15 statements using a 5-point scale. The mucolytic agents evaluated were carbocysteine, erdosteine and N-acetylcysteine (NAC). Data were collected anonymously and consensus presented using descriptive statistics. RESULTS: The 47 respondents reached consensus on the statements. They agreed that regular treatment with mucolytic agents effectively reduces the frequency of exacerbations, reduces the duration of mild-to-moderate exacerbations, and can increase the time to first exacerbation and symptom-free time in COPD patients. Consensus was consistently highest for erdosteine. The experts agreed that all three mucolytics display antioxidant and anti-inflammatory activity. Erdosteine and NAC were thought to improve the efficacy of some classes of antibacterial drugs. All three mucolytics were considered effective for the short-term treatment of symptoms of acute exacerbations when added to other drugs. The panel agreed that approved doses of mucolytic agents have favorable side-effect profiles and can be recommended for regular use in patients with a bronchitic phenotype. CONCLUSIONS: Consensus findings support the wider use of mucolytic agents as add-on therapy for COPD. However, the differences in pharmacological actions and clinical effectiveness must be considered when deciding which mucolytic to use.


Assuntos
Acetilcisteína/uso terapêutico , Carbocisteína/uso terapêutico , Consenso , Expectorantes/uso terapêutico , Guias de Prática Clínica como Assunto , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Exacerbação dos Sintomas , Tioglicolatos/uso terapêutico , Tiofenos/uso terapêutico , Acetilcisteína/administração & dosagem , Acetilcisteína/efeitos adversos , Carbocisteína/administração & dosagem , Carbocisteína/efeitos adversos , Quimioterapia Combinada , Expectorantes/administração & dosagem , Expectorantes/efeitos adversos , Feminino , Nível de Saúde , Humanos , Internacionalidade , Masculino , Inquéritos e Questionários , Tioglicolatos/administração & dosagem , Tioglicolatos/efeitos adversos , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Resultado do Tratamento
3.
Physiotherapy ; 108: 78-87, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32721607

RESUMO

OBJECTIVES: To explore and describe current UK physiotherapy practice relating to airway clearance techniques and mucoactive agents in critically ill adult patients with acute respiratory failure in the intensive care unit. DESIGN: A descriptive, qualitative study using focus group interviews. Focus groups were audio-recorded, independently transcribed, and data analysed thematically. Participants Senior, experienced physiotherapists, clinically active in critical care. RESULTS: Fifteen physiotherapists participated in four interview sessions. Five themes emerged describing airway clearance techniques: 'Repertoire of airway clearance techniques', 'Staffing and skillset', 'Commencing respiratory physiotherapy', 'Technique selection', and 'Determining effectiveness' were themes related to airway clearance techniques. Five themes were also identified in relation to mucoactive agents: 'Use in clinical practice', 'Decision to commence', 'Selection of agent', 'Stopping mucoactive agents', and 'Determining effectiveness'. A summary of key features of standard practice was developed. CONCLUSIONS: Standard UK physiotherapy practice of airway clearance techniques is variable, but patient-centred and targeted to individual need, with adjunctive use of mucoactive agents to enhance and optimise patient management if required. Based on this study, key features of airway clearance techniques have been summarised to help capture standard care, which could be used in future trials involving ACT as part of usual care.


Assuntos
Carbocisteína/uso terapêutico , Estado Terminal/reabilitação , Modalidades de Fisioterapia , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/reabilitação , Terapia Respiratória/métodos , Adulto , Terapia Combinada , Expectorantes/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Pesquisa Qualitativa , Reino Unido
5.
Xenobiotica ; 50(1): 51-63, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31233370

RESUMO

1. Consistent differences in the proportion of an orally administered dose of S-carboxymethyl-l-cysteine subsequently excreted in the urine as S-oxide metabolites were reported 40 years ago. This observation suggested the existence of inter-individual variation in the ability to undertake the enzymatic S-oxygenation of this compound. Pedigree studies and investigations employing twin pairs indicated a genetically controlled phenomenon overlaid with environmental influences. It was reproducible and not related to gender or age.2. Studies undertaken in several healthy volunteer cohorts always provided similar results that were not significantly different when statistically analysed. However, when compared to these healthy populations, a preponderance of subjects exhibiting the characteristic of poor sulfoxidation of S-carboxymethyl-l-cysteine was found within groups of patients suffering from various disease conditions. The most striking of these associations were witnessed amongst subjects diagnosed with neurodegenerative disorders; although, underlying mechanisms were unknown.3. Exhaustive investigation has identified the enzyme responsible for this S-oxygenation reaction as the tetrahydrobiopterin-dependent aromatic amino acid hydroxylase, phenylalanine 4-monooxygenase classically assigned the sole function of converting phenylalanine to tyrosine. The underlying principle is discussed that enzymes traditionally associated solely with intermediary metabolism may have as yet unrecognised alternative roles in protecting the organism from potential toxic assault.


Assuntos
Fenilalanina Hidroxilase/metabolismo , Carbocisteína/análogos & derivados , Carbocisteína/metabolismo , Humanos , Fenilalanina/metabolismo , Fenilalanina Hidroxilase/genética , Polimorfismo Genético
6.
J Dermatol ; 47(2): 174-177, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31840853

RESUMO

Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe hypersensitivity drug reaction affecting the skin and multiple internal organ systems. We report a 47-year-old man with DIHS/DRESS and comorbidities (fulminant type 1 diabetes mellitus, valsartan-induced photosensitivity, vitiligo and acute interstitial nephritis). Although acute interstitial nephritis usually appears in the early phase, his is a rare case of acute interstitial nephritis more than 2 years after the onset of DIHS/DRESS.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/complicações , Fadiga/tratamento farmacológico , Nefrite Intersticial/diagnóstico , Acetaminofen/efeitos adversos , Biópsia , Carbocisteína/efeitos adversos , Claritromicina/efeitos adversos , Creatinina/sangue , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/patologia , Quimioterapia Combinada/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Muramidase/efeitos adversos , Nefrite Intersticial/sangue , Nefrite Intersticial/etiologia , Nefrite Intersticial/patologia , Prednisolona/uso terapêutico , Pele/patologia , Fatores de Tempo
7.
Am J Otolaryngol ; 41(1): 102315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31732313

RESUMO

PURPOSE: Chronic cough is a common complaint. Because the pathophysiology of chronic cough is complicated, the management of chronic cough is challenging. To the best of our knowledge, no previous study has examined the effect of macrolide antibiotics in chronic cough patients with chronic rhinosinusitis. The purpose of this study is to determine the changes in lung function for chronic cough patients with chronic rhinosinusitis who are treated by clarithromycin and carbocisteine. MATERIALS AND METHODS: Thirty-two chronic cough patients with chronic rhinosinusitis were recruited. Patients using inhaled corticosteroids and/or a bronchodilator, asthmatic patients, and patients with abnormal findings on auscultation and/or chest X-ray examination were excluded from this study. The patients received low-dose clarithromycin treatment for 3 months. Both before and after the treatment, a computed tomography (CT) scan of the paranasal sinuses, lung function test, peripheral blood test, and sino-nasal outcome test (SNOT-20) were applied. RESULTS: Both the lung function and Lund-MacKay CT scores were improved by the long-duration therapy with macrolide antibiotics. The change in obstructive pulmonary function and the improvement of the CT score in each subject were significantly correlated. SNOT scores also improved after the treatment. CONCLUSIONS: The macrolide antibiotics treatment has beneficial effects on lung function in non-asthmatic chronic cough patients with normal chest X-ray findings. The improvement of chronic rhinosinusitis may have some role in the lung condition. Upper respiratory tract examination and treatment may be useful for the management of chronic cough.


Assuntos
Antibacterianos/uso terapêutico , Anti-Infecciosos Locais/uso terapêutico , Carbocisteína/uso terapêutico , Claritromicina/uso terapêutico , Tosse/tratamento farmacológico , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Doença Crônica , Tosse/fisiopatologia , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Índice de Gravidade de Doença
8.
Laryngoscope ; 130(5): E289-E297, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31294840

RESUMO

OBJECTIVE: Carbocisteine (CCis), a mucoactive agent, is used to improve the symptoms of sinonasal diseases. However, the effect of CCis on nasal ciliary beating remains uncertain. We examined the effects of CCis on ciliary beat distance (CBD, an index of amplitude), and ciliary beat frequency (CBF) in ciliated human nasal epithelial cells (cHNECs) in primary culture. METHODS: The cHNECs were prepared from the nasal tissue resected from patients required surgery for chronic sinusitis (CS) or allergic rhinitis (AR). CBD and CBF were measured using videomicroscopy equipped with a high-speed camera. RESULTS: CCis increased CBD by 30%, but not CBF, and decreased intracellular Cl- concentration ([Cl- ]i ) in cHNECs. The CCis' actions were mimicked by the Cl- -free NO3 - solution. In contrast, prior treatment of NPPB (20 µM) or CFTR(inh)-172 (1 µM), which increased [Cl- ]i by 20%, decreased CBF by 10% and CBD by 25% and inhibited the CCis' actions. However, prior treatment of T16Ainh-A01 (10 µM) did not inhibit the CCis' actions, although it decreased [Cl- ]i by 10% and CBD by 15%. Thus, CCis stimulates Cl- channels including cystic fibrosis transmembrane conductance regulator (CFTR). Moreover, CCis enhanced the transport of microbeads driven by the beating cilia in cHNECs. The CCis actions were similar in cHNECs from both types of pateints. CONCLUSION: CCis increased CBD by 30% in cHNECs via an [Cl- ]i decrease stimulated by activation of Cl- channels, including CFTR. CCis may stimulate nasal mucociliary clearance by increasing CBD in patients contracting CS or AR. LEVEL OF EVIDENCE: NA. Laryngoscope, 130:E289-E297, 2020.


Assuntos
Carbocisteína/farmacologia , Cílios/efeitos dos fármacos , Depuração Mucociliar/efeitos dos fármacos , Mucosa Nasal/diagnóstico por imagem , Sinusite/tratamento farmacológico , Células Cultivadas , Cílios/metabolismo , Cílios/patologia , Células Epiteliais/efeitos dos fármacos , Humanos , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Transdução de Sinais , Sinusite/metabolismo , Sinusite/patologia
9.
Trials ; 20(1): 747, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856887

RESUMO

BACKGROUND: Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care. METHODS: This is a 52-week, 2 × 2 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care - the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750 mg three times per day until visit 3, reducing to 750 mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria are as follows: adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum. DISCUSSION: This trial's pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE. TRIAL REGISTRATION: EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017). ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018. Funder: National Institute for Health Research, Health Technology Assessment Programme (15/100/01). SPONSOR: Belfast Health and Social Care Trust. Ethics Reference Number: 17/NE/0339. Protocol version: v3.0 Final_14052018.


Assuntos
Bronquiectasia/tratamento farmacológico , Carbocisteína/administração & dosagem , Análise Custo-Benefício , Expectorantes/administração & dosagem , Solução Salina Hipertônica/administração & dosagem , Administração por Inalação , Adulto , Carbocisteína/agonistas , Esquema de Medicação , Quimioterapia Combinada/economia , Quimioterapia Combinada/métodos , Expectorantes/economia , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Nebulizadores e Vaporizadores , Ensaios Clínicos Controlados Aleatórios como Assunto , Solução Salina Hipertônica/economia , Escarro/efeitos dos fármacos , Resultado do Tratamento
10.
Drug Des Devel Ther ; 13: 3259-3268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571828

RESUMO

Background: Cigarette smoke (CS) results in chronic mucus hypersecretion and airway inflammation, contributing to COPD pathogenesis. Mucin 5B (MUC5B) and mucin 5 AC (MUC5AC) are major mucins implicated in COPD pathogenesis. Carbocisteine can reduce mucus viscosity and elasticity. Although carbocisteine decreased human elastase-induced MUC5AC expression in vitro and reduced MUC5AC expression that alleviated bacteria adhesion and improved mucus clearance in vivo, the roles of carbocisteine in inducing MUC5B expression in COPD remain unclear. Methods: To investigate the Muc5b/Muc5ac ratio and the gene and protein levels of Muc5b in COPD and carbocisteine intervention models. C57B6J mice were used to develop COPD model by instilling intratracheally with lipopolysaccharide on days 1 and 14 and were exposed to CS for 2 hr twice a day for 12 weeks. Low and high doses of carbocisteine 112.5 and 225 mg/kg/d, respectively, given by gavage administration were applied for the treatment in COPD models for the same duration, and carboxymethylcellulose was used as control. Carbocisteine significantly attenuated inflammation in bronchoalveolar lavage fluid and pulmonary tissue, improved pulmonary function and protected against emphysema. Results: High-dose carbocisteine significantly decreased the overproduction of Muc5b (P<0.01) and Muc5ac (P<0.001), and restored Muc5b/Muc5ac ratio in COPD model group (P<0.001). Moreover, the Muc5b/Muc5ac ratio negatively correlated with pro-inflammatory cytokines such as IL-6 and keratinocyte-derived cytokine, mean linear intercept, functional residual capacity and airway resistance, but positively correlated with dynamic compliance. Conclusions: These findings suggest that carbocisteine attenuated Muc5b and Muc5ac secretion and restored Muc5b protein levels, which may improve mucus clearance in COPD.


Assuntos
Carbocisteína/uso terapêutico , Mucina-5AC/metabolismo , Mucina-5B/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Quimiocinas/metabolismo , Fumar Cigarros/efeitos adversos , Modelos Animais de Doenças , Enfisema/prevenção & controle , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/administração & dosagem , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Muco/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia
11.
Eur Rev Med Pharmacol Sci ; 23(15): 6727-6735, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31378916

RESUMO

OBJECTIVE: COPD is one of the major causes of morbidity and mortality worldwide and represents one of the most important issues for public health. Frequent exacerbations induce a faster decline in lung function and poorer quality of life, increase mortality, and have a socio-economic impact with a high burden in terms of resources and healthcare costs. The clinical trials evaluated the effect of mucolytics in COPD and showed that the long-term carbocysteine, associated with bronchodilators, anticholinergics, and steroids, reduces the frequency of exacerbations and improves the quality of life. PATIENTS AND METHODS: The aim of this prospective real-life study was to evaluate the long-term impact on exacerbations (at 1 year) in COPD patients treated with carbocysteine lysine salt (single dose of 2.7 g once a day) in addition to background therapy with or without inhaled steroids. RESULTS: In a total of 155 evaluable patients, our study showed that the addition of a single dose of carbocysteine lysine salt to background therapy determines a statistically significant reduction of the average number of exacerbations vs. the number observed in the previous year (from 1.97±0.10 to 1.03±0.11; p<0.01), irrespective of treatment with or without inhaled steroids. In particular, in patients with ≥2 exacerbations in the previous year, the addition of carbocysteine lysine salt resulted in a statistically significant reduction in the exacerbations rate from 69% to 33% and from 58% to 25%, respectively (p<0.01) in patients with or without inhaled steroids. CONCLUSIONS: In summary, our data highlighted the efficacy of long-term administration of a single daily dose of carbocysteine lysine salt (2.7 g/day) in reducing the number and rate of exacerbations in COPD patients, independently from the use of inhaled steroids.


Assuntos
Broncodilatadores/administração & dosagem , Carbocisteína/análogos & derivados , Expectorantes/administração & dosagem , Glucocorticoides/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbocisteína/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Qualidade de Vida , Índice de Gravidade de Doença , Exacerbação dos Sintomas , Resultado do Tratamento
12.
Respir Res ; 20(1): 104, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133026

RESUMO

BACKGROUND: To date there are no head-to-head studies comparing different mucolytic/antioxidant agents. Considering the inconsistent evidence resulting from the pivotal studies on mucolytic/antioxidant agents tested in chronic obstructive pulmonary disease (COPD), and the recent publication of Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD (RESTORE) study, we have performed a meta-analysis to compare the efficacy and safety of erdosteine 600 mg/day, carbocysteine 1500 mg/day, and N-acetylcysteine (NAC) 1200 mg/day in COPD. METHODS: A pairwise and network meta-analyses were performed to assess the efficacy of erdosteine, carbocysteine, and NAC on acute exacerbation of COPD (AECOPD), duration of AECOPD, and hospitalization. The frequency of adverse events (AEs) was also investigated. RESULTS: Data obtained from 2753 COPD patients were extracted from 7 RCTs published between 2004 and 2017. In the pairwise meta-analysis mucolytic/antioxidant agents significantly reduced the risk of AECOPD (RR 0.74 95%CI 0.68-0.80). The network meta-analysis provided the following rank of effectiveness: erdosteine>carbocysteine>NAC. Only erdosteine reduced the risk of experiencing at least one AECOPD (P < 0.01) and the risk of hospitalization due to AECOPD (P < 0.05). Erdosteine and NAC both significantly reduced the duration of AECOPD (P < 0.01). The AEs induced by erdosteine, carbocysteine, and NAC were mild in severity and generally well tolerated. The quality of evidence of this quantitative synthesis is moderate. CONCLUSIONS: The overall efficacy/safety profile of erdosteine is superior to that of both carbocysteine and NAC. Future head-to-head studies performed on the same COPD populations are needed to definitely confirm the results of this meta-analysis. TRIAL REGISTRATION: CRD42016053762 .


Assuntos
Acetilcisteína/uso terapêutico , Antioxidantes/uso terapêutico , Carbocisteína/uso terapêutico , Expectorantes/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tioglicolatos/uso terapêutico , Tiofenos/uso terapêutico , Acetilcisteína/efeitos adversos , Antioxidantes/efeitos adversos , Carbocisteína/efeitos adversos , Expectorantes/efeitos adversos , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Tioglicolatos/efeitos adversos , Tiofenos/efeitos adversos , Resultado do Tratamento
14.
Yakugaku Zasshi ; 139(2): 299-308, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30713242

RESUMO

To clarify the volume of water required to paste pediatric powders, we herein established a standard for the powder paste state by measuring yield values when water was added to powders. The powders used in the present study were selected from 8 types including original and generic drugs. Tipepidine hibenzate is prescribed in the pediatric field in combination with ambroxol hydrochloride and l-carbocysteine. The volumes of water needed to achieve the paste state of ambroxol hydrochloride between the original and generic drugs were similar. However, the volumes of water needed for l-carbocysteine markedly differed between the original and generic drugs due to differences in their additives. The spreadability of the mixture when water was added to the powders was evaluated using a spread meter. Among the powders tested in the present study, the yield value to achieve a paste state with the addition of water was approximately 1000 dyne/cm2. The optimum volume of water estimated from this yield value using the linear proportional relationship for the amount of powder may be applied to the mixture of each pediatric power for dosage/body weight.


Assuntos
Composição de Medicamentos/métodos , Composição de Medicamentos/normas , Medicamentos Genéricos , Pomadas , Pós , Água , Adjuvantes Farmacêuticos , Ambroxol , Carbocisteína , Pomadas/normas , Piperidinas , Pós/normas
15.
Xenobiotica ; 49(4): 495-502, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29648495

RESUMO

Mice that were heterozygous dominant for the enu1 and enu2 mutation in phenylalanine monooxygenase/phenylalanine hydroxylase (PAH) resulted in hepatic PAH assays for S-carboxymethyl-L-cysteine (SCMC) that had significantly increased calculated Km (wild type (wt)/enu1, 1.84-2.12 fold increase and wt/enu2 a 2.75 fold increase in PAH assays). The heterozygous dominant phenotypes showed a significantly reduced catalytic turnover of SCMC (wt/enu1, 6.11 fold decrease and wt/enu2 an 11.25 fold decrease in calculated Vmax). Finally, these phenotypes also had a significantly reduced clearance, CLE (wt/enu1, 13.02 fold and wt/enu2, a 30.80-30.94 fold decrease) The homozygous recessive phenotype (enu1/enu1) was also found to have significantly increased calculated Km (2.16 fold increase), a significantly reduced calculated Vmax (11.35-12.33 fold decrease) and CLE (24.75-25.00 fold decrease). The enu2/enu2, homozygous recessive phenotype had no detectable PAH activity using SCMC as substrate. The identity of the enzyme responsible for the C-oxidation of L-phenylalanine (L-Phe) and the S-oxidation of SCMC in wt/wt (BTBR) mice was identified using monoclonal antibody and selective chemical inhibitors and was found to be PAH. This in vitro mouse hepatic cytosolic fraction metabolism investigation provides further evidence to support the hypothesis that an individual possessing one variant allele for PAH will result in a poor metaboliser phenotype that is unable to produce significant amounts of S-oxide metabolites of SCMC.


Assuntos
Carbocisteína/metabolismo , Citosol/metabolismo , Fígado/metabolismo , Fenilcetonúrias/metabolismo , Animais , Feminino , Cinética , Masculino , Camundongos , Camundongos Mutantes , Oxirredução , Fenilalanina/metabolismo , Fenilalanina Hidroxilase/antagonistas & inibidores , Fenilalanina Hidroxilase/metabolismo , Especificidade por Substrato
16.
J Nippon Med Sch ; 85(4): 215-220, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30259890

RESUMO

BACKGROUND: The influence of S-carboxymethylcystein (S-CMC) on the proliferation ability of goblet cells in nasal polyp epithelium in response to inflammatory stimulation was examined. METHODS: The subjects were patients with chronic paranasal sinusitis. An epithelial cell culture system was established using nasal polyp mucosa excised during endoscopic paranasal sinus surgery. The samples were divided into 4 groups (group a: control group, group b: 10 ng/mL tumor necrosis factor-α (TNF-α) treatment group, group c: 10-7 M S-CMC and 10 ng/mL TNF-α treatment group, group d: 10-5 M S-CMC and 10 ng/mL TNF-α treatment group). The total number of epithelial cells and number of goblet cells were measured under a microscope, and the ratio of goblet cells to the total number of epithelial cells was calculated. RESULTS: In group b, 10 ng/mL of TNF-α significantly increased the number of goblet cells compared with group a, suggesting involvement of TNF-α in goblet cell proliferation. In addition, the number of goblet cells significantly decreased in group d compared with that in group b, and it also decreased in group c compared with that in group b, although the difference was not significant, and the decrease was smaller than that in group d, suggesting that S-CMC inhibited goblet cell proliferation in a concentration-dependent manner. CONCLUSION: TNF-α promoted goblet cell proliferation in nasal polyps, suggesting its influence on nasal polyp formation. As S-CMC inhibited inflammatory stimulation-induced goblet cell proliferation in nasal polyp epithelium, it may be useful for the treatment of sinusitis.


Assuntos
Carbocisteína/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/patologia , Células Caliciformes/patologia , Adulto , Idoso , Carbocisteína/uso terapêutico , Células Cultivadas , Doença Crônica , Depressão Química , Relação Dose-Resposta a Droga , Humanos , Mediadores da Inflamação/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/citologia , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Seios Paranasais/patologia , Sinusite/tratamento farmacológico , Sinusite/patologia , Fator de Necrose Tumoral alfa/efeitos adversos , Adulto Jovem
17.
Pediatr Dermatol ; 35(6): e357-e359, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30152557

RESUMO

N-acetylcysteine in combination with urea is effective for the treatment of congenital ichthyosis. Although it is well tolerated, its foul smell may compromise treatment adherence. Carbocysteine is a similar molecule without that bad odor. Thus, we have tried a new formula with carbocysteine for the treatment of 4 patients with ichthyosis, with positive results.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Carbocisteína/administração & dosagem , Ictiose/tratamento farmacológico , Administração Tópica , Criança , Pré-Escolar , Combinação de Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Ureia/administração & dosagem
18.
J Pharm Pharmacol ; 70(8): 1069-1077, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29882598

RESUMO

OBJECTIVES: To determine the Km , Vmax , cofactor, activator and inhibitor requirements of human cysteine dioxygenase and S-carboxymethyl-l-cysteine S-oxygenase with respect to both l-Cysteine and S-carboxymethyl-l-cysteine as substrates. METHODS: In vitro human hepatic cytosolic fraction enzyme assays were optimised for cysteine dioxygenase activity using l-Cysteine as substrate and the effect of various cofactors, activators and inhibitors on the S-oxidations of both l-Cysteine and S-carboxymethyl-l-cysteine were investigated. KEY FINDINGS: The results of the in vitro reaction phenotyping investigation found that although both cysteine dioxygenase and S-carboxymethyl-l-cysteine S-oxygenase required Fe2+ for catalytic activity both enzymes showed considerable divergence in cofactor, activator and inhibitor specificities. Cysteine dioxygenase has no cofactor but uses NAD+ and NADH(H+ ) as pharmacological chaperones and is not inhibited by S-carboxymethyl-l-cysteine. S-carboxymethyl-l-cysteine S-oxygenase requires tetrahydrobiopterin as a cofactor, is not activated by NAD+ and NADH(H+ ) but is activated by l-Cysteine. Additionally, the sulfydryl alkylating agent, N-ethylmaleimide, activated carboxymethyl-l-cysteine S-oxygenase but inhibited cysteine dioxygenase. CONCLUSIONS: Human hepatic cytosolic fraction cysteine dioxygenase activity is not responsible for the S-oxidation of the substituted cysteine, S-carboxymethyl-l-cysteine.


Assuntos
Carbocisteína/metabolismo , Cisteína Dioxigenase/metabolismo , Cisteína/metabolismo , Citosol/metabolismo , Fígado/metabolismo , Citosol/enzimologia , Feminino , Humanos , Técnicas In Vitro , Fígado/ultraestrutura , Oxirredução , Especificidade por Substrato
19.
Food Chem ; 260: 283-288, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29699671

RESUMO

The majority of l-cysteine is obtained industrially by hydrolysis of animal materials, such as poultry feathers. Despite widespread belief, there is little evidence that human hair is used as a source material and its use is explicitly banned in the European Union (2000/63/EC decision). We developed an isotope ratio mass spectrometric (EA-IRMS) method to determine carbon and nitrogen isotopic ratio in cysteine preparations and related compounds, e.g. cystine and carbocysteine. A threshold relying on the 15N/14N was established to differentiate between hair and feathers; a value below 6.6‰ indicates a poultry feathers origin. Global uncertainty of measurement was found to be 0.1‰ for δ15N (sample size of 0.5-1.8 mg).


Assuntos
Cisteína/análise , Plumas/química , Cabelo/química , Espectrometria de Massas/métodos , Isótopos de Nitrogênio/análise , Animais , Carbocisteína/análise , Escherichia coli/química , Europa (Continente) , Humanos , Aves Domésticas , Reprodutibilidade dos Testes
20.
Med Glas (Zenica) ; 14(2): 182-188, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28786969

RESUMO

Aim To investigate the effects of carbocisteine treatment in the reduction of frequency of productive cough episodes, preventing disease progression and improving the quality of life as well as the tolerability of the administered treatment and patient compliance during the study. Methods This observational, non-interventional, multicenter, cohort study included 501 patients with chronic obstructive pulmonary disease (COPD) who were administrated carbocisteine capsules 375 mg and followed up during the next 15 days. The patients were observed at 3 points, baseline and two additional assessments. General clinical condition of patients, along with the spirometry testing at all three points were examined. Thr quality of life was assessed on the 1st and 3rd observation with Leicester Cough Questionnaire. Tolerability and patient compliance were measured throughout the study. Results There was a significant change of forced expiratory volume in 1 second (FEV1) status between the second and third observation (p=0.002). Examination of general symptoms showed a statistically significant reduction in cough by 74.9%, in sputum production by 48.5%, in dyspnea by 29% and in fatigue by 50%. After the administration of carbocisteine the median value of overall quality of life was 3.79 (3.63 - 3.89). Conclusion 375mg carbocisteine capsules were found to be effective and well-tolerated in the treatment of COPD, with a small percentage of reported mild adverse reactions and with a significant improvement of quality of life.


Assuntos
Carbocisteína/uso terapêutico , Expectorantes/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/psicologia
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