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 JovemRESUMO
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 TratamentoRESUMO
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 TratamentoRESUMO
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 TratamentoRESUMO
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 & dosagemRESUMO
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic and progressive lung disease characterized by irreversible airflow obstruction, airway inflammation, oxidative stress and, often, mucus hypersecretion. The aim of this study is to determine if carbocisteine, a mucolytic and antioxidant agent, administered daily for 12 months, can reduce exacerbation frequency in COPD patients. METHODS: This observational study was conducted in Naples (population approximately 1000,000), Italy. It included 85 out-patients (mean age of 67.8 ± 8.6 years) followed by Clinic of Respiratory Diseases of the University Federico II. Every patient underwent spirometry demonstrating airflow obstruction not fully reversible according to ERS/ATS criteria for COPD diagnosis (Tiffenau index less than 70% after administration of salbutamol, a beta2 agonist drug). Patients enrolled had diagnosed COPD since 2 years and suffered at least one exacerbation in the previous year. None of the patients had been treated with carbocisteine or other mucolytic agent for a longer period of time than 7 days and no more than 4 times in the previous year to the enrollment. All of them assumed daily 2.7 g of carbocisteine lysine salt for a year in addition to their basic therapy. RESULTS: The comparison of exacerbation frequency between the previous year (T0) and the end of study treatment (T12), documents a statistically significant reduction of exacerbations(number of exacerbations at T0: 2 [1,3] vs number of exacerbations at T12: 1 [1,2]; p < 0.001).Quality of life was also reported and showed a statistically significant improvement at the end of the study (p < 0.001).We did not find correlation between reducing exacerbation frequency and exposure to cigarette smoking, passive smoking exposure in childhood, the use of inhaled steroids, the level of education of our patients and the GOLD stadium. INTERPRETATION: Daily administration of a mucolytic drug such as carbocisteine for prolonged periods in addition to the bronchodilator therapy can be considered a good strategy for reducing exacerbation frequency in COPD.
Assuntos
Carbocisteína/análogos & derivados , Expectorantes/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Idoso , Broncodilatadores/uso terapêutico , Carbocisteína/administração & dosagem , Carbocisteína/uso terapêutico , Expectorantes/administração & dosagem , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fumar/epidemiologia , Espirometria , Fatores de TempoRESUMO
The objective of the present study was to improve the effectiveness of medicamental therapy of exudative otitis media in the children with recurrent and chronic adenoiditis. It was shown that the use of fluifort (carbocysteine lysine salt) for the treatment of exudative otitis media in the children presenting with chronic adenoiditis is a more effective approach in comparison with the expectant management. It is concluded that the application of carbocysteine lysine salt in combination with the mometasone furoate nasal spray ensures the rapid elimination of the symptoms of adenoiditis and significantly accelerates the resolution of exudative otitis media compared with the monotherapeutic treatment.
Assuntos
Tonsila Faríngea/patologia , Anti-Infecciosos Locais/farmacologia , Anti-Inflamatórios/farmacologia , Carbocisteína/farmacologia , Nasofaringite/tratamento farmacológico , Otite Média com Derrame/tratamento farmacológico , Pregnadienodiois/farmacologia , Tonsila Faríngea/efeitos dos fármacos , Anti-Infecciosos Locais/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Carbocisteína/administração & dosagem , Criança , Pré-Escolar , Doença Crônica , Comorbidade , Quimioterapia Combinada , Humanos , Furoato de Mometasona , Nasofaringite/epidemiologia , Otite Média com Derrame/epidemiologia , Pregnadienodiois/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum viscosity, increase airway clearance of sputum, reduce infection and inflammation and improve lung function. Thiol derivatives, either oral or nebulized, have shown benefit in other respiratory diseases. Their mode of action is likely to differ according to the route of administration. There are several thiol derivatives, and it is unclear which of these may be beneficial in cystic fibrosis. OBJECTIVES: To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, hand searches of relevant journals, abstract books and conference proceedings.Most recent search: 13 June 2013.We also conducted a PubMed search on 26 February 2013 for relevant published articles. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing nebulized or oral thiol derivatives to placebo or another thiol derivative in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently assessed trials for inclusion, analysed risk of bias and extracted data. MAIN RESULTS: Searches identified 23 trials; nine trials (255 participants) are included, of these seven trials are more than 10 years old. Three trials of nebulized thiol derivatives were identified (one compared 20% N-acetylcysteine to 2% N-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.Six trials of oral thiol derivatives were identified. Three trials compared N-acetylcysteine to placebo; one compared N-acetylcysteine, ambroxol and placebo; one compared carbocysteine to ambroxol; and one compared low and high-dose N-acetylcysteine. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. AUTHORS' CONCLUSIONS: We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.
Assuntos
Acetilcisteína/administração & dosagem , Ambroxol/administração & dosagem , Carbocisteína/administração & dosagem , Fibrose Cística/tratamento farmacológico , Expectorantes/administração & dosagem , Administração por Inalação , Administração Oral , Fibrose Cística/complicações , Glutationa/administração & dosagem , Humanos , Pneumopatias/tratamento farmacológico , Depuração Mucociliar/efeitos dos fármacos , Nebulizadores e Vaporizadores , Ensaios Clínicos Controlados Aleatórios como Assunto , Solução Salina Hipertônica/administração & dosagemAssuntos
Carbocisteína/efeitos adversos , Febre/induzido quimicamente , Idoso , Carbocisteína/administração & dosagem , Carbocisteína/metabolismo , Ritmo Circadiano , Esquema de Medicação , Expectorantes/administração & dosagem , Expectorantes/efeitos adversos , Expectorantes/metabolismo , Feminino , Febre/metabolismo , Humanos , Testes do EmplastroRESUMO
BACKGROUND AND OBJECTIVE: Carbocysteine (S-carboxymethylcysteine) is a mucoactive drug with in vitro free radical scavenging and anti-inflammatory properties. Several clinical trials have indicated that carbocysteine reduces exacerbation rates in COPD. In the present study, the effect of carbocysteine on the airway load of Haemophilus influenzae was assessed in rats chronically exposed to cigarette smoke (CS). In addition, the effects of carbocysteine on airway mucus hypersecretion and mucociliary clearance (MCC) associated with the adherence and clearance of H. influenzae were investigated. METHODS: Wistar rats were randomly divided into control, carbocysteine vehicle, CS exposure and carbocysteine treatment groups. After 12 weeks, rats were selected for quantitative inoculation of H. influenzae. BAL fluid and lungs were collected aseptically after 3 h for quantitative culture of H. influenzae. MCC was measured by quantifying the clearance of (99m)Tc-Sc. Goblet cell metaplasia and the presence of mucoid matter were evaluated by Alcian blue/periodic acid-Schiff staining. Mucin 5AC (Muc5AC) expression was detected by western blotting and real-time reverse transcription-PCR. RESULTS: Exposure to CS increased airway H. influenzae load, aggravated mucus hypersecretion and delayed MCC. Treatment with carbocysteine decreased airway H. influenzae load, and attenuated airway mucus hypersecretion, with improved MCC associated with adherence and clearance of H. influenzae. CONCLUSIONS: These results suggest that carbocysteine may be beneficial in patients with COPD by increasing the clearance of bacteria and decreasing bacterial load.
Assuntos
Aderência Bacteriana/efeitos dos fármacos , Carbocisteína/administração & dosagem , Expectorantes/administração & dosagem , Infecções por Haemophilus/tratamento farmacológico , Haemophilus influenzae/efeitos dos fármacos , Nicotiana/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/microbiologia , Fumaça/efeitos adversos , Animais , Carga Bacteriana/efeitos dos fármacos , Células Caliciformes/efeitos dos fármacos , Haemophilus influenzae/isolamento & purificação , Masculino , Depuração Mucociliar/efeitos dos fármacos , Muco/efeitos dos fármacos , Muco/microbiologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ratos , Ratos Wistar , Fumar/efeitos adversos , Resultado do TratamentoAssuntos
Acetilcisteína , Carbocisteína , Expectorantes , Infecções Respiratórias/tratamento farmacológico , Acetilcisteína/administração & dosagem , Bronquite/tratamento farmacológico , Carbocisteína/administração & dosagem , Contraindicações , Comparação Transcultural , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Europa (Continente) , Expectorantes/administração & dosagem , França , Humanos , Lactente , Fatores de RiscoRESUMO
BACKGROUND AND PURPOSE: Montelukast and S-carbocysteine have been used in asthmatic patients as an anti-inflammatory or mucolytic agent respectively. S-carbocysteine also exhibits anti-inflammatory properties. EXPERIMENTAL APPROACH: Ovalbumin (OVA) sensitized BALB/c mice were challenged with OVA for 3 days followed by single OVA re-challenge (secondary challenge) 2 weeks later. Forty-eight hours after secondary challenge, mice were assessed for airway hyperresponsiveness (AHR) and cell composition in bronchoalveolar lavage (BAL) fluid. Suboptimal doses of 10 mg.kg(-1) of S-carbocysteine by intraperitoneal injection (ip), 20 mg.kg(-1) of montelukast by gavage, the combination of S-carbocysteine and montelukast or 3 mg.kg(-1) of dexamethasone as a control were administered from 1 day before the secondary challenge to the last experimental day. Isolated lung cells were cultured with OVA and montelukast to determine the effects on cytokine production. KEY RESULTS: Treatment with S-carbocysteine or montelukast reduced both AHR and the numbers of eosinophils in BAL fluid. Neutralizing IFN-gamma abolished the effects of S-carbocysteine on these airway responses. Combination of the two drugs showed further decreases in both AHR and eosinophils in the BAL fluid. Goblet cell metaplasia and Th2-type cytokines, interleukin (IL)-4, IL-5 and IL-13, in BAL fluid were decreased with montelukast treatment. Conversely, S-carbocysteine increased Th1-type cytokines, IFN-gamma and IL-12 in BAL fluid. CONCLUSIONS AND IMPLICATIONS: The combination of two agents, montelukast and S-carbocysteine, demonstrated additive effects on AHR and airway inflammation in a secondary allergen model most likely through independent mechanisms of action.
Assuntos
Acetatos/farmacologia , Hiper-Reatividade Brônquica/tratamento farmacológico , Carbocisteína/farmacologia , Quinolinas/farmacologia , Acetatos/administração & dosagem , Animais , Antiasmáticos/administração & dosagem , Antiasmáticos/farmacologia , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Hiper-Reatividade Brônquica/imunologia , Líquido da Lavagem Broncoalveolar , Carbocisteína/administração & dosagem , Ciclopropanos , Dexametasona/farmacologia , Sinergismo Farmacológico , Quimioterapia Combinada , Eosinófilos/metabolismo , Feminino , Inflamação/tratamento farmacológico , Inflamação/imunologia , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Quinolinas/administração & dosagem , SulfetosRESUMO
The aim of this study was to investigate the feasibility of employing S-carboxymethyl-L-cysteine as a treatment of chronic obstructive pulmonary disease in dogs. To this end the pharmacokinetic parameters of orally administered S-carboxymethyl-L-cysteine were determined in the dog, cow and sheep. Six healthy beagle dogs, six endogenous Greek sheep and four Holstein Fresian calves were orally dosed with 10 mg/kg body weight of S-carboxymethyl-L-cysteine. No significant differences in T(max) and T(1/2) were reported between the species. However, significantly higher AUC((0-last)), 21.56+/-6.67 microg h ml(-1) and AUC((0-infinity)), 21.63+/-6.68 microg h ml(-1) were seen in the dogs compared to the sheep and calves. The calculated V(D) was significantly higher in the sheep (10.4+/-2.7 L kg(-1)) and the calves (3.8+/-0.7 L kg(-1)) compared to the dogs (1.0+/-0.6 L kg(-1)). The rank order of increasing C(L) was sheep (3.4+/-2.7 L h(-1)kg(-1))>calves (2.7+/-0.4 L h(-1) kg(-1))>dogs (0.5+/-0.2 L h(-1)kg(-1)). The result for the dogs was significantly lower that the calculated C(L) for the sheep and calves. All these results indicate that the oral administration of S-carboxymethyl-L-cysteine may be useful during the therapeutic management of chronic obstructive pulmonary disease in dogs.
Assuntos
Carbocisteína/administração & dosagem , Carbocisteína/farmacocinética , Administração Oral , Animais , Carbocisteína/sangue , Bovinos , Cães , Masculino , Ovinos , Especificidade da Espécie , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologiaRESUMO
BACKGROUND: Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum viscosity, increase airway clearance of sputum, reduce infection and inflammation and improve lung function. Thiol derivatives, either oral or nebulized, have shown benefit in other respiratory diseases. Their mode of action is likely to differ according to the route of administration. There are several thiol derivatives, and it is unclear which of these may be beneficial in cystic fibrosis. OBJECTIVES: To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, hand searches of relevant journals, abstract books and conference proceedings.Most recent search: November 2008. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing nebulized or oral thiol derivatives to placebo or another thiol derivative in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently assessed trials for inclusion, analysed methodological quality and extracted data. MAIN RESULTS: Searches identified 18 trials; eight (seven older than 10 years) (234 participants) are included. Three trials of nebulized thiol derivatives were identified (one compared 20% n-acetylcysteine to 2% n-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.Five studies of oral thiol derivatives were identified. Three studies compared n-acetylcysteine to placebo; one compared n-acetylcysteine, ambroxol and placebo; and one compared carbocysteine to ambroxol. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. AUTHORS' CONCLUSIONS: We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.
Assuntos
Acetilcisteína/administração & dosagem , Ambroxol/administração & dosagem , Carbocisteína/administração & dosagem , Fibrose Cística/tratamento farmacológico , Expectorantes/administração & dosagem , Administração por Inalação , Administração Oral , Fibrose Cística/complicações , Humanos , Pneumopatias/tratamento farmacológico , Depuração Mucociliar/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
1. The effects of s-carboxymethyl-L-cysteine (S-CMC), either administered orally to rats or incubated with tissue preparations from rats and humans, on isometric contractions of tracheal smooth muscle were investigated in the present study using an improved in vitro model of tracheal tube or ring preparations. The involvement of the tracheal epithelium in the observed effects was also investigated. 2. The experimental model permitted selective perfusion of the airway tube, luminal-IN or serosal-OUT, and measurement of airway smooth muscle contraction or relaxation in preparations with (+) or without (-) epithelium (Ep), excluding direct effects of airway mucus. 3. We found that oral pretreatment of rats with S-CMC (mixed with water; 200 mg/kg per day for 2 weeks), but not short pre-incubation of preparations in vitro (10(-3) mol/L S-CMC for 1 h), diminished the sensitivity of -Ep preparations to carbachol compared with controls (EC(50) (-log(10) mol/L) values: 5.5 +/- 0.1 vs 5.8 +/- 0.1, respectively, for IN perfusion (P < 0.005); 5.6 +/- 0.1 vs 5.9 +/- 0.1, respectively, for OUT perfusion (P < 0.005)), whereas the sensitivity of preparations to aminophylline was not affected. Normal sensitivity to carbachol stimulation was re-established if preparations were pre-incubated with capsaicin. 4. It was also found that longer pre-incubation (4 h) of ring-preparations of human bronchus with S-CMC (10(-5) mol/L) in vitro resulted in a diminished response to carbachol stimulation. 5. In conclusion, S-CMC had small inhibitory effects on the sensitivity of rat and human airway smooth muscle to carbachol, particularly in endothelium-denuded preparations. Whether the epithelium was responding to S-CMC by producing some contracting factor(s) requires further investigation.
Assuntos
Broncoconstrição/efeitos dos fármacos , Carbacol/farmacologia , Carbocisteína/farmacologia , Mucosa Respiratória/fisiologia , Animais , Carbocisteína/administração & dosagem , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Traqueia/efeitos dos fármacos , Traqueia/fisiologiaRESUMO
Prescription of mucoactive drugs for chronic obstructive pulmonary disease (COPD) is increasing. This development in clinical practice arises, at least in part, from a growing understanding of the important role that exacerbation frequency, systemic inflammation and oxidative stress play in the pathogenesis of respiratory disease. S-carboxymethylcysteine (carbocisteine) is the most frequently prescribed mucoactive agent for long-term COPD use in the UK. In addition to its mucoregulatory activity, carbocisteine exhibits free-radical scavenging and anti-inflammatory properties. These characteristics have stimulated interest in the potential that this and other mucoactive drugs may offer for modification of the disease processes present in COPD. This article reviews the pharmacology, in vivo and in vitro properties, and clinical trial evidence for carbocisteine in the context of guidelines for its use and the current understanding of the pathogenic processes that underlie COPD.
Assuntos
Anti-Inflamatórios/uso terapêutico , Carbocisteína/análogos & derivados , Carbocisteína/uso terapêutico , Expectorantes/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Carbocisteína/administração & dosagem , Carbocisteína/efeitos adversos , Ensaios Clínicos como Assunto , Esquema de Medicação , Expectorantes/administração & dosagem , Expectorantes/efeitos adversos , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/efeitos adversos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Guias de Prática Clínica como Assunto , Doença Pulmonar Obstrutiva Crônica/metabolismo , Resultado do TratamentoRESUMO
The bioequivalence of two carbocysteine capsulae preparations was assessed in 18 healthy volunteers who received a single 750 mg dose of each carbocysteine formulation, and a new sensitive method for the quantification of carbocysteine in human plasma was developed. The study was conducted using an open, randomized, two-sequence, two-period crossover design with a week washout period between the succesive treatments. Plasma samples were obtained over a 12-hour period and analyzed by high performance liquid chromatography coupled to electrospray ionization-mass spectrometry. Either a multiplicative statistic model for concentration-dependent parameters or an additive approach for time-related parameters were used for the comparison of pharmacokinetic parameters describing both the early and total exposure to carbocysteine. The respective 90% confidence limits [CL] of the individual ratios of geometric means were 0.898 to 1.112 [point estimate 0.999] for Cmax and 0.923 to 1.210 [point estimate 1.057] for AUC(0-infinity), while the difference between times elapsed to reach Cmax was insignificant [p = 0.4497]. Since both 90% CL for the log-transformed AUC(0-infinity) and Cmax geometric mean ratios were included in the proposed 0.80-1.25 interval, test drug (Bronchobos capsules) was considered bioequivalent to the reference one (Mucopront capsules).
Assuntos
Antitussígenos/administração & dosagem , Antitussígenos/farmacocinética , Carbocisteína/administração & dosagem , Carbocisteína/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Cápsulas , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Composição de Medicamentos , Medicamentos Genéricos , Cromatografia Gasosa-Espectrometria de Massas , Meia-Vida , Humanos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Equivalência TerapêuticaRESUMO
PURPOSE: To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support, antioxidants, and drugs, all given orally, in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress. PATIENTS AND METHODS: An open early-phase II study was designed according to the Simon two-stage design. The integrated treatment consisted of diet with high polyphenols content (400 mg), antioxidant treatment (300 mg/d alpha-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C), and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib. The treatment duration was 4 months. The following variables were evaluated: (a) clinical (Eastern Cooperative Oncology Group performance status); (b) nutritional [lean body mass (LBM), appetite, and resting energy expenditure]; (c) laboratory [proinflammatory cytokines and leptin, reactive oxygen species (ROS) and antioxidant enzymes]; (d) quality of life (European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D, and MFSI-SF). RESULTS: From July 2002 to January 2005, 44 patients were enrolled. Of these, 39 completed the treatment and were assessable. Body weight increased significantly from baseline as did LBM and appetite. There was an important decrease of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha, and a negative relationship worthy of note was only found between LBM and IL-6 changes. As for quality of life evaluation, there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D(VAS), and multidimensional fatigue symptom inventory-short form scores. At the end of the study, 22 of the 39 patients were "responders" or "high responders." The minimum required was 21; therefore, the treatment was effective and more importantly was shown to be safe. CONCLUSION: The efficacy and safety of the treatment have been shown by the study; therefore, a randomized phase III study is warranted.
Assuntos
Anorexia/dietoterapia , Caquexia/dietoterapia , Suplementos Nutricionais , Neoplasias/complicações , Apoio Nutricional/métodos , Adulto , Idoso , Anorexia/etiologia , Ácido Ascórbico/administração & dosagem , Caquexia/etiologia , Carbocisteína/administração & dosagem , Celecoxib , Ácidos Docosa-Hexaenoicos/administração & dosagem , Feminino , Humanos , Modelos Lineares , Masculino , Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Estresse Oxidativo , Pirazóis/administração & dosagem , Estatísticas não Paramétricas , Sulfonamidas/administração & dosagem , Ácido Tióctico/administração & dosagem , Resultado do Tratamento , Vitamina A/administração & dosagem , Vitamina E/administração & dosagemAssuntos
Carbocisteína/administração & dosagem , Carbocisteína/farmacocinética , Expectorantes/administração & dosagem , Expectorantes/farmacocinética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Safrol/análogos & derivados , Biotransformação , Cronoterapia , Humanos , Safrol/farmacocinética , Resultado do TratamentoRESUMO
Chronic obstructive pulmonary disease (COPD) is characterized by an airways inflammation and by an enhanced generation of reactive oxygen species. The aim of our study was to assess the inflammation and the oxidative stress in airways of COPD patients with acute exacerbation of disease and in stability. Furthermore, we investigated the anti-inflammatory and antioxidant effects of 6 months treatment with carbocysteine lysine salt monohydrate (SCMC-Lys) in COPD. We studied 30 mild acute COPD, 10 mild stable COPD and 15 healthy subjects. 8-isoprostane and Interleukine-6 were measured in their breath condensate through immunoassay. Significantly higher concentrations of exhaled 8-isoprostane and Interleukine-6 were found in acute COPD patients compared to stable COPD and healthy controls (21.8+/-5.1 vs. 13.2+/-2.0 vs. 4.7+/-1.8 pg/ml and 7.4+/-0.9 vs. 5.8+/-0.2 vs. 2.7+/-0.6 pg/ml, p<0.0001). COPD patients treated with SCMC-Lys showed a marked reduction of exhaled 8-isoprostane and Interleukine-6 (8.9+/-1.5 and 4.6+/-0.8 pg/ml, p<0.0001). These findings suggest that there is an increase of 8-isoprostane and Interleukine-6 concentrations in the breath condensate of COPD patients compared to healthy controls especially during acute exacerbations of the disease. Moreover, we showed an anti-inflammatory and antioxidant effect of short-term administration of SCMC-Lys in COPD, suggesting the importance of a further placebo-controlled study that should evaluate the effects of this drug.