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At least 19 recordsLinked to original sources
PubMed2001

Effects of carbocysteine on antigen-induced increases in cough sensitivity and bronchial responsiveness in guinea pigs.

Carbocysteine is a mucoactive drug and is being used for both acute and chronic infectious airway diseases. Although carbocysteine can repair the damage of epithelial cells caused by exposure to various agents, the effects of this agent on allergic airway diseases such as asthma and eosinophilic bronchitis with an isolated chronic cough, in both of which epithelial damage may be characteristic, is not clear. We investigated the effects of carbocysteine on antigen-induced cough hypersensitivity to inhaled capsaicin at 48 h and bronchial hyperresponsiveness to inhaled methacholine at 72 h after challenge with an aerosolized antigen in actively sensitized guinea pigs. After measuring bronchial responsiveness, we examined neutral endopeptidase (NEP) activity in the tracheal tissue. Carbocysteine (10, 30, or 100 mg/kg) was given intraperitoneally every 12 h for 3 days after antigen challenge. The number of coughs elicited by an aerosol of capsaicin (10(-4) M) was significantly (p < 0.01) decreased in carbocysteine groups (6.13 +/- 0.59 at 10 mg/kg, 4.88 +/- 0.67 at 30 mg/kg, and 4.50 +/- 0.33 at 100 mg/kg during 3 min measurement) compared with the control group (9.75 +/- 0.53). Furthermore, carbocysteine dose dependently repaired the antigen-induced decrease of NEP activity in the tracheal tissue, but it did not influence the bronchial hyperresponsiveness or bronchoalveolar lavage cell component. These findings suggest that carbocysteine promotes the repair of damaged epithelium by allergic reaction and may be useful in allergic airway diseases accompanied by isolated chronic coughing, especially eosinophilic bronchitis without asthma and tracheobronchitis with cough hypersensitivity.

Administration, Inhalation↗
PubMedDate not supplied

Relative bioavailability of carbocysteine from three dosage forms, investigated in healthy volunteers.

The aim of the present study was to evaluate the bioavailability of a new tablet formulation of carbocysteine relative against two other oral carbocysteine containing dosage forms, viz. a syrup and capsules. Plasma levels and urine concentrations of carbocysteine were monitored, following oral administration of all three dosage forms to healthy human volunteers, by direct derivatization of carbocysteine using dabsylchloride and subsequent high performance liquid chromatography. There was no difference in bioavailability of carbocysteine from these dosage forms as expressed by the respective areas under the plasma concentration-time curves and total amounts of unchanged carbocysteine excreted in urine.

Administration, Oral↗
PubMed2006

High-throughput determination of carbocysteine in human plasma by liquid chromatography/tandem mass spectrometry: application to a bioequivalence study of two formulations in healthy volunteers.

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method to determine carbocysteine in human plasma was developed and fully validated. After methanol-induced protein precipitation of the plasma samples, carbocysteine was subjected to LC/MS/MS analysis using electrospray ionization (ESI). The MS system was operated in the selected ion monitoring (SRM) mode. Chromatographic separation was performed on a Hypurity C18 column (i.d. 2.1 mm x 50 mm, particle size 5 microm). The method had a chromatographic running time of 2.0 min and linear calibration curves over the concentration ranges of 0.1-20 microg/mL for carbocysteine. The lower limit of quantification (LLOQ) of the method was 0.1 microg/mL for carbocysteine. The intra- and inter-day precision was less than 7% for all quality control samples at concentrations of 0.5, 2.0, and 10.0 microg/mL. These results indicate that the method was efficient with a simple preparation procedure and a very short running time (2.0 min) for carbocysteine compared with methods reported in the literature and had high selectivity, acceptable accuracy, precision and sensitivity. The validated LC/MS/MS method has been successfully used to a bioequivalence study of two tablet formulations of carbocysteine in healthy volunteers.

Blood Chemical Analysis↗
PubMed2003

Effect of carbocysteine on cough reflex to capsaicin in asthmatic patients.

AIMS: Cough, one of the main symptoms of bronchial asthma, is a chronic airway inflammatory disease with functionally damaged bronchial epithelium. Recently, we established an animal model with cough hypersensitivity after antigen challenge and clearly showed the protective effect of carbocysteine in this model. This study was designed to investigate the clinical effect of carbocysteine for cough sensitivity in patients with bronchial asthma. METHODS: The effects of the two orally active mucoregulatory drugs, carbocysteine and ambroxol hydrochloride, on cough response to inhaled capsaicin were examined in 14 patients with stable asthma. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough sensitivity. RESULTS: Geometric mean values of the cough threshold at run-in (baseline) and after 4 weeks' treatment of placebo, 1500 mg day-1 of carbocysteine and 45 mg day-1 of ambroxol hydrochloride were 12.8 micro M (95% confidence interval [CI] 5.5, 29.6), 11.0 micro M (95% CI 4.4, 27.5), 21.0 micro M (95% CI 8.8, 50.2) and 11.6 micro M (95% CI 5.8, 23.3), respectively. The cough threshold for carbocysteine was significantly greater than those of ambroxol hydrochloride (P = 0.047) and placebo (P = 0.047), respectively. CONCLUSIONS: These findings indicate that carbocysteine administration may be a novel therapeutic option for asthmatic patients, especially with cough variant asthma.

Adult↗
PubMed2003

Determination of carbocysteine in human plasma by liquid chromatography/tandem mass spectrometry employing precolumn derivatization.

A sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed to determine carbocysteine in human plasma using 2-pyridylacetic acid as the internal standard (IS). The method employed derivatization with 10 M hydrochloric acid/methanol, which significantly improved the ionization efficiency of carbocysteine. After methanol-induced protein precipitation of plasma samples, carbocysteine and the IS were derivatized and subjected to LC/MS/MS analysis using atmospheric pressure chemical ionization. The method has a lower limit of quantitation of 20 ng/mL for a 0.2-mL plasma aliquot. The intra- and inter-day precision (RSD), calculated from quality control (QC) samples, was less than 7%. The accuracy, determined using QC samples, was within +/- 1%. The method offered increased sensitivity, selectivity and speed of analysis over existing methods. The method was utilized to support clinical pharmacokinetic studies of carbocysteine in volunteers following oral administration.

Calibration↗
PubMed2006

A comparative bioavailability study of a generic capsule formulation containing carbocysteine.

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).

Antitussive Agents↗
PubMed1985

Comparison between penetration of amoxicillin combined with carbocysteine and amoxicillin alone in pathological bronchial secretions and pulmonary tissue.

Patients with chronic bronchitis were treated orally with either amoxicillin (500 mg) alone or in combination with carbocysteine (150 mg), thrice daily for five days, in order to assess whether the combination allows higher antibiotic levels to be obtained in bronchial mucus than those obtained from amoxicillin alone. Serum and mucus levels were determined for each patient at first and fifth day of the two drug regimens. The levels of amoxicillin in the lung tissue collected in patients undergoing pulmonary surgery were also determined after a single oral dose of amoxicillin (1 g) or of amoxicillin (1 g) plus carbocysteine (300 mg). In the bronchial secretions, at the same plasma concentrations, amoxicillin levels were statistically higher after administration of combined substances. These findings indicate the presence of a pharmacokinetic synergism between these compounds, which allows amoxicillin to penetrate more easily through the hemato-bronchial barrier. The association of amoxicillin and carbocysteine, determining an increase of the quantitative levels of antibiotic in the bronchial secretion (also if it is purulent), performs a sterilizing action in a short time with significant therapeutic advantages.

Aged↗
PubMed1990

Long-lasting effects on rheology and clearance of bronchial mucus after short-term administration of high doses of carbocysteine-lysine to patients with chronic bronchitis.

The rheological behavior and clearance of bronchial mucus samples collected by protected expectoration from 24 out-patients with simple chronic bronchitis were investigated before, at the end of a short period of treatment (4 days) with a single oral dose of 2.7 g (sachet) of carbocysteine-lysine (evening meal), and on the 4th and 8th days after the end of treatment versus placebo. In the group treated with carbocysteine-lysine, there were significant reductions in viscosity (-67, -48, -62%) and increases in mucociliary transport (+41, +31, +34%) at the three times mentioned. The most striking finding was that the improvements were still present 8 days after cessation of treatment. The elasticity parameter was not affected in any statistically significant way (-10, -24, +65%). These findings suggest the presence of some type of 'post-mucoactive' effect.

Adult↗
PubMedDate not supplied

Carbocysteine.

Carbocysteine is prescribed for conditions characterized by the accumulation of excessive mucus. Although often described as a mucolytic, its function is probably that of mucoregulation, which results in physical changes in accumulated secretions that are favorable in terms of clearance. The chemistry, pharmacology, pharmacokinetics, clinical applications, and toxicology of carbocysteine are reviewed.

Carbocysteine↗
PubMed1992

[Carbocysteine in the treatment of recurrent bronchitis in infants].

In a group of 51 children aged 6-24 months the therapeutic effectiveness of the mucolytic preparation carbocysteine was tested and compared with the effect of Ipeca syrup. The effect was evaluated by means of a point score comprising changes of the clinical picture of the disease and the use of other laboratory examinations. The results of the examination revealed the more favourable effect of carbocysteine, as compared with a mixture of Ipeca syrup in the treatment of acute relapsing bronchitis in infants.

Bronchitis↗
PubMed1978

Determination of carbocysteine from human plasma.

A fast and accurate GLC procedure for determining carbocysteine, using a sulfur photometric detector, is described. Interferences from nonsulfur constituents are eliminated. The method is linear from 2 to 15 micrograms. Results from the application of this method to a bioavailability study in humans are given.

Biological Availability↗
PubMed1995

Effectiveness of carbocysteine lysine salt monohydrate on models of airway inflammation and hyperresponsiveness.

We investigated the possible effects of the mucoactive drug Carbocysteine lysine salt monohydrate (CLS.H2O) on experimentally-induced airway inflammation and hyperresponsiveness. CLS.H2O given by the oral route (300 mg kg(-1)) significantly reduced neutrophil infiltration into the airway lumen induced by intratracheal injection of IL-1 beta in rats. In addition, CLS.H2O inhibited dose-dependently (100-300 mg kg(-1) p.o.) the formation of pleural exudate and leukocyte recruitment induced by intrapleural injection of carrageenan in rats. Because of the close interaction between the inflammatory process and the development of airway hyperresponsiveness we also tested CLS.H2O on cigarette-smoke-induced inflammation and hyperreactivity in anaesthetized guinea-pigs. The drug, given either by oral (300 mg kg(-1)) or aerosol route (30-100 mg ml(-1)), was able to reduce the increase in airway responsiveness induced by smoke and the associated cell recruitment detected in the bronchoalveolar lavage (BAL) fluids. These results suggest that CLS.H2O can exert an anti-inflammatory action in addition to its mucoregulatory activity. The anti-inflammatory and anti-hyperreactivity effect of the drug within the airways may be of advantage in the treatment of inflammatory lung diseases where mucus secretion together with airway inflammation and hyperreactivity contribute to airway obstruction.

Acetylcholine↗
PubMed2004

Exhaled Interleukine-6 and 8-isoprostane in chronic obstructive pulmonary disease: effect of carbocysteine lysine salt monohydrate (SCMC-Lys).

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.

Adult↗
PubMed1997

S-carbocysteine-lysine salt monohydrate and cAMP cause non-additive activation of the cystic fibrosis transmembrane regulator channel in human respiratory epithelium.

S-Carbocysteine-lysine salt monohydrate (S-CMC-Lys) has been shown to open a Cl- channel in the trachea, thus aiding fluid secretion. The aim of this study was to characterize the channel and the action mechanism on a culture line of human respiratory epithelial cells. The patch-clamp technique (in cell-attached or inside-out configuration) and conventional micro-electrodes were used. The activity and density of a cAMP-dependent Cl- channel, identical to the cystic fibrosis transmembrane regulator (CFTR) channel, proved to be maximally stimulated by 100 microM S-CMC-Lys present in the cAMP-free cell incubation medium for 240-290 min (cell-attached configuration). Subsequent addition of cAMP to the medium did not determine any further activation. S-CMC-Lys acted mostly indirectly as, when placed in direct contact with a membrane patch, activation of the CFTR channel was nil (cytoplasmic side) or limited (external side).

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Prevention of acute exacerbations of chronic obstructive bronchitis with carbocysteine lysine salt monohydrate: a multicenter, double-blind, placebo-controlled trial.

The efficacy and safety of carbocysteine lysine salt monohydrate (SCMC-Lys) in the prevention of acute exacerbations associated with chronic obstructive bronchitis were evaluated in a multicenter double-blind, placebo-controlled, parallel group trial in 662 outpatients. After a 1-month run-in period, patients were randomized to three groups and assigned to receive one of the following oral treatments: continuous SCMC-Lys 2.7 g once daily, intermittent SCMC-Lys at the same dosage (1-week courses alternating with 1-week intervals on placebo) or placebo. Each treatment lasted for 6 months and spanned the cooler months of the year. Evaluation was based on a daily recording of relevant clinical symptoms and signs and subsequent evaluation of the collected data by three blinded independent physicians. A total of 146 patients (23%) failed to complete the 6-month treatment (mostly due to difficulties in complying with protocol requirements), without clear-cut differences in the dropout rate in the three groups. An intention-to-treat analysis revealed that the incidence of patients without exacerbations in the group assigned to continuous SCMC-Lys treatment was significantly higher than in the placebo-treated group (p < 0.001). The total number of patients with at least one exacerbation was 66 (29.6%) in the group treated with continuous SCMC-Lys compared with 100 (45.9%) with placebo. In the former group the time between initiation of treatment and first exacerbation was significantly prolonged. The average number of days with acute respiratory illness was significantly decreased in the group receiving continuous SCMC-Lys compared with the group receiving placebo, and this was associated with a significant reduction in the antibiotic consumption during the trial period. In patients assigned to intermittent treatment, results of the assessed endpoints did not differ significantly from those observed in the placebo group. No serious adverse effects were reported. It is concluded that continuous administration of SCMC-Lys throughout the winter season is effective in preventing acute exacerbations in patients with chronic obstructive bronchitis and it is well tolerated.

Adult↗
PubMedDate not supplied

The management of cystic fibrosis with carbocysteine lysine salt: single-blind comparative study with ambroxol hydrochloride.

The effectiveness of carbocysteine lysine salt monohydrate (SCMC-Lys) and ambroxol hydrochloride (ABX) in the management of respiratory impairment was compared in a single-blind, randomized study of 26 cystic fibrosis patients with similar baseline characteristics. Adults received either SCMC-Lys 900 mg or ABX 33 mg three times a day and children under 14 years of age either SCMC-Lys 270 mg three times a day or ABX 10 mg four times a day. All treatments were given orally for 80 days and at the end of this control period both groups showed significant improvement in chest sound score but improvement in cough score was observed only in those receiving SCMC-Lys. Expectorate viscosity and elasticity decreased significantly in both groups. In SCMC-Lys-treated patients paCO2 decreased and paO2 and Hb O2 saturation increased while only paO2 increased significantly in those treated with ABX. An increase in tidal volume, peak expiratory flow values and forced expiratory volume were evident in those receiving SCMC-Lys while significant increases in forced expiratory flow were recorded in those receiving ABX. SCMC-Lys patient's Shwachmann index improved significantly and conversely to the ABX patients. No adverse events were recorded in either treatment group. The study concluded that SCMC-Lys is at least as effective as ABX in improving respiratory function in patients with cystic fibrosis.

Adolescent↗
PubMed2001

Antioxidant activity of carbocysteine lysine salt monohydrate.

BACKGROUND: Reactive oxygen radicals are involved in many respiratory diseases, including chronic obstructive pulmonary disease (COPD). Carbocysteine lysine salt monohydrate (CLS) is a mucoactive drug effective in the treatment of bronchopulmonary diseases characterized by mucus alterations, including COPD. In the present study, the antioxidant activity of CLS was studied in vitro in three different oxygen radical producing systems, i.e. bronchoalveolar lavages (BAL) from patients affected by COPD, ultrasound treated human serum and cultured human lung endothelial cells challenged with elastase. METHODS: BAL, exposed or not to different concentrations of CLS (1.5-30 mM), was assayed for free radical content by fluorometric analysis of DNA unwinding (FADU) or by cytochrome c reduction kinetics. Human serum was treated with ultrasound in the presence or absence of CLS (1.5, 2.5 mM) or N-acetyl cysteine (NAC; 4, 5 mM) and assayed for free radical content by FADU. Human endothelial cells cultured in vitro from pulmonary artery were incubated with elastase (0.3 IU/mL), in the presence or absence of glutathione (GSH; 0.65 mM) or CLS (0.16 mM). The supernatant was tested for cytochrome c reduction kinetics whereas cell homogenates were assessed for xanthine oxidase (XO) content by SDS-PAGE. RESULTS: Results showed that CLS is more effective as an in vitro scavenger in comparison to GSH and NAC. CLS reduced the damage of DNA from healthy donors exposed to COPD-BAL and was able to quench clastogenic activity induced in human serum by exposure to ultrasound at concentrations as low as 2.5 mM. NAC protect DNA from radical damage, starting from 5 mM. In human lung endothelial cells cultured in presence of elastase, CLS (0.16 mM) decreased xanthine oxidase activity. CONCLUSIONS: These results suggest that CLS could act by interfering with the conversion of xanthine dehydrogenase into superoxide-producing xanthine oxidase. The antioxidant activity of CLS could contribute to its therapeutic activity by reducing radical damage to different lung structures.

Aged↗
PubMedDate not supplied

Carbocysteine lysine salt monohydrate (SCMC-LYS) is a selective scavenger of reactive oxygen intermediates (ROIs).

Carbocysteine lysine salt monohydrate (SCMC-Lys) is a well-known mucoactive drug whose therapeutic efficacy is commonly related to the ability of SCMC-Lys to replace fucomucins by sialomucins. The aim of this study was to determine if SCMC-Lys could exert an anti-oxidant action by scavenging reactive oxygen intermediates (ROIs). Our results show that SCMC-Lys proved effective as a selective scavenger of hypochlorous acid (HOCl) and hydroxyl radical (OH.), this effect being related to the reactivity of the SCMC tioether group. The scavenger activity of SCMC-Lys was observed in free cellular system as well as in activated human polymorphonuclear neutrophils (PMNs). SCMC-Lys scavenger activity on HOCl was paralleled by a powerful protection from HOCl-mediated inactivation of alpha1-antitripsin (alpha1-AT) inhibitor, the main serum protease inhibitor. Production of interleukin-(IL-)8, a major mediator of PMN recruitment in inflammatory diseases, is known to be mediated by intracellular OH. SCMC-Lys significantly reduced IL-8 production on stimulated human peripheral blood mononuclear cells (PBMCs) in the same range of concentrations affecting OH. activity. It is concluded that SCMC-Lys could exert, in addition to its mucoactive capacity, an anti-oxidant action, thus contributing to the therapeutic efficacy of SCMC-Lys.

Carbocysteine↗