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PubMed1981

[Effect of bromhexine on the tracheal secretory cells with enhanced mucus synthesis by pilocarpine treatment (author's transl)].

The effects of bromhexine on secretory activities of canine tracheal secretory cells with stimulated synthesis of acid glycoprotein (AGP) by pilocarpine 10(-6)M treatment an on behaviour of glycoprotein in these secretory cells were investigated histologically and histochemically. Following bromhexine treatment, the number of total glycoprotein-containing goblet cells (GC) remained unchanged. The numbers of AGP-containing and sulphated glycoprotein (SGP)-containing GC significantly decreased, while neutral glycoprotein (NGP)-containing GC significantly increased. The acinar inner diameter of the submucosal gland and the acinar inner diameter of this gland to wall ratio slightly increased. Thickness of the acinus and Reid index slightly decreased, concentration-dependently. AGP and SGP content in glandular cells decreased, while NGP content in these cells markedly increased. Bromhexine 10(-5) and 10(-4)M treatment resulted in increased total saccharide and protein concentrations in the incubation fluid, whereas the agent significantly decreased N-acetylhexosamine, in a concentration-dependent manner. These findings suggest that while bromhexine does not stimulate secretory activities of GC, it does slightly stimulate the activities of the submucosal glands. Bromhexine markedly dissolves AGP in the granules of these secretory cells.

Animals↗
PubMed1975

Effect of bromhexine on the incidence of postoperative bronchopneumonia after upper abdominal surgery.

The incidence of postoperative bronchopneumonia in 70 patients undergoing upper abdominal surgery who received intramuscular and oral bromhexine after operation for 5 days was 25% (8 of 32), compared with 34% (13 of 38) in a control group, but this difference in favour of bromhexine does not reach statistical significance. All patients had postoperative physiotherapy. However, in a high-risk group (patients who smoked more than 10 cigarettes a day, who admitted to a productive cough before the operation and in whom the forced expiratory volume as a percentage of the forced vital capacity was less than 70) the incidence of postoperative bronchopneumonia in those who had bromhexine was 6 of 17 compared with 9 of 15 in the controls. Thus bromhexine for the prevention and treatment of postoperative bronchopneumonia in high-risk patients after upper abdominal surgery deserves further study.

Adult↗
PubMed2000

Acute generalized exanthematous pustulosis associated with polysensitivity to paracetamol and bromhexine: the diagnostic role of in vitro interferon-gamma release test.

We report a patient with acute generalized exanthematous pustulosis (AGEP), which occurred 3 days after ingesting paracetamol and bromhexine. Both were immediately stopped and the rash resolved rapidly. To determine the offending drug responsible for AGEP, an in vitro drug-induced interferon (IFN)-gamma release test was performed using an ELISA technique. Increased IFN-gamma release was observed following in vitro challenge of the patient's lymphocytes with paracetamol or bromhexine (110% and 157% increase, respectively). In vitro challenge with paracetamol or bromhexine in a control patient, treated with paracetamol and bromhexine, did not induce an increase in IFN-gamma. These findings suggest that the patient with AGEP may have polysensitivity to both drugs. The ELISA assessment also demonstrates the relevance of in vitro cytokine release tests in the investigation of such dermatoses.

Acetaminophen↗
PubMed2005

Effect of bromhexine hydrochloride therapy for alcoholic chronic pancreatitis.

BACKGROUND: Abstinence is a prerequisite for the treatment of alcoholic chronic pancreatitis, but there are patients who have repeated attacks because of their inability to abstain and the consequent congestive effects of the continued alcohol intake on pancreatic juice. Bromhexine hydrochloride, a bronchial mucolytic, has an affinity for acinar cells and causes them to secrete pancreatic juice of low viscosity. METHODS: Twelve patients with alcoholic chronic pancreatitis, who were unable to abstain from drinking, were administered bromhexine hydrochloride for 6 months to assess its therapeutic efficacy. RESULTS: Of 12 patients administered bromhexine, 8 (67%) reported symptomatic improvement, and all patients showed improvement in the levels of pancreatic enzymes. Pancreatic exocrine function also tended to improve, but no improvement of pancreatic endocrine function was detected. Although none of the pancreatic stones present in some patients disappeared, a protein plug present in one patient disappeared, accompanied by improvement in the irregular outline of the lumen of the main pancreatic duct. CONCLUSION: Bromhexine hydrochloride may be a new for the morbidity of chronic pancreatitis, in which there is increased viscosity of the pancreatic juice and formation of a protein plug.

Bromhexine↗
PubMedDate not supplied

Oral bromhexine has no effect on tear and lysosyme secretion in healthy subjects.

The purpose of the present study was to determine whether bromhexine (Solvex) affects the rate of tear secretion or the concentration of lysosyme in the tear fluid in healthy subjects. The rate of tear secretion and lysosyme concentration in tear fluid were estimated in 56 healthy volunteers before and after 3 weeks of oral administration of placebo (tablets of vitamin C, 200 mg per day) followed by bromhexine tablets, 32 mg per day. Shirmer's test I was performed to evaluate the tear secretion, and the lysosyme plate method was used to detect lysosyme concentration. Shirmer's test showed similar results before and after placebo and bromhexine administration. In conclusion, oral bromhexine was found to have no effect on the rate of tear secretion, nor on the concentration of lysosyme in the tear fluid of healthy subjects.

Administration, Oral↗
PubMed1985

[Modulation of alveolar macrophage activity by ambroxol, bromhexine and exogenous arachidonic acid].

The increased generation of reactive oxygen metabolites (ROM) (O2-, H2O2, 1O2, X OH, OX-) by alveolar macrophages (AM) and neutrophils has been proposed as an important step in the pathogenesis of many acute and chronic lung disorders. With regard to a possible therapeutic application in this context the effect of bromhexine and ambroxol on the activity of AM of of guinea-pigs and of patients with lung diseases was investigated. The activity of AM, which were isolated by bronchoalveolar lavage, was determined by means of chemiluminescence (CL)-measuring. Ambroxol and bromhexine cause a depression of the spontaneous as well as of the induced CL [yeast cell walls, yeast glucan, exogenous arachidonic acid (AA)] of AM. AM from guinea-pigs and in some cases also from patients show primarily an increase of the CL-signal under the influence of bromhexine. These results suggest that ambroxol and bromhexine reduce the production of ROM by AM. The mechanism is possibly due to the activation of acyl-CoA-lysophosphatide acyltransferase. The increase of this enzyme activity lowers the intracellular concentration of the free AA, whereby the generation of ROM is diminished too. The investigations exhibit a new possibility of influence of respiratory burst and thus indirectly of AA-liberation from phospholipids. The probable reduction of AA-liberation by these drugs could also be of importance for other lung cells especially concerning the biosynthesis of eicosanoids (AA-metabolites), which play an important part as pathogenetic mediators in different lung diseases.

Ambroxol↗
PubMed1988

Lack of detectable DNA alkylation for bromhexine in man.

It is known that in vitro incubation of the expectorant drug bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) with nitrite yields methylcyclohexyl nitrosamine (NMCA). NMCA is capable of methylating DNA when administered to rats. In vivo tests with bromhexine have also demonstrated that the drug methylates DNA when it is orally administered in the presence of sodium nitrite, presumably due to the intragastric formation of NMCA. In this study the potential of bromhexine to methylate nucleic acids in man, under physiological conditions, has been investigated. 20 volunteers were orally administered on each of three successive days 48 mg of bromhexine hydrochloride, labelled with three deuterium atoms in the N-methyl group. Urine was collected before treatment and subsequent to the last dose, and analysed by GC-MS for d0- and d3-7-methylguanine. 7-Methylguanine is naturally occurring in urine owing to the turnover of t-RNA of which it is a minor constituent. It is also a repair product from nucleic acids methylated by carcinogens, which is known to be excreted unmetabolised largely within 24 h of the methylation process. Unlabelled 7-methylguanine was present at levels of 7.36 +/- 2.43 mg/d in control urine and 6.12 +/- 2.36 mg/d in treated urine, in accord with previously published values. The excretion of isotopically labelled 7-methylguanine averaged 0.43 +/- 0.077% of the unlabelled concentration for control urines and 0.44 +/- 0.066% for treated urines, i.e. no d3-7-methylguanine could be detected following the drug treatment. The observed signals were largely accounted for by the naturally occurring isotopes 13C and 15N.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Nitrosation of bromhexine and aminophenazone in gastric juice after high nitrate loading in the diet. An ex-vivo/in-vitro study in humans.

In an ex-vivo study, nitrosation of bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) in human gastric fluid under conditions of high dietary nitrate intake was investigated. 26 healthy volunteers received 200 mg of nitrate in a vegetable during a standard breakfast. Nitrite values in saliva were significantly increased 2 to 3 h after nitrate intake. In contrast, nitrite levels in gastric fluid sampled 3 h after nitrate intake remained in the low concentration range of less than or equal to 1.7 micrograms/No2-/ml. Incubation of gastric fluid samples at 37 degrees C with the recommended maximum single oral dose of bromhexine (16 mg/100 ml) or an equimolar concentration of aminophenazone revealed in 4/26 cases formation of N-nitrosomethylcyclohexylamine from bromhexine at barely detectable levels. In contrast, aminophenazone generated N-nitrosodimethylamine at a very high rate, resulting in yields of greater than 50% in several samples. In view of the average daily background exposure to preformed nitrosamines in foods (0.5-1 microgram/capita), according to these results the possible contribution of in-vivo nitrosation of bromhexine corresponds at best to 10% in addition to the daily background exposure and therefore can be regarded as negligible.

Aminopyrine↗
PubMed1981

[Histological and histochemical changes of tracheal secretory cells following bromhexine treatment (author's transl)].

The effects of bromhexine, a mucolytic agent, on secretory activities of canine tracheal secretory cells and on behaviour of glycoprotein in these secretory cells were investigated histologically and histochemically. Following bromhexine treatment, the number of total glycoprotein-containing goblet cells (GC) remained the same. The number of acid glycoprotein (AGP)-containing GC was reduced concentration-dependently, while neutral glycoprotein (NGP)-containing GC significantly increased with doses of 10-6, 10-5 and 10-4M. The number of sulphated glycoprotein (SGP) in AGP-containing GC decreased concentration-dependently. Acinar inner diameter of the submucosal gland and an acinar inner diameter of this gland to wall ratio (AIWR) increased with doses of 10-5 and 10-4M. Particularly, AIWR significantly increased with dose of 10-4M. Thickness of the acinus tended to slightly decrease concentration-dependently. AGP content in glandular cells decreased, while NGP content in these cells markedly increased, concentration-dependently. SGP content in the glandular cells decreased. Total saccharide and protein concentrations in the incubation fluid significantly increased with higher concentrations of the treatment, whereas N-acetylhexosamine slightly decreased concentration-dependently. These findings suggest that bromhexine does not enhance secretory activities of GC, but does stimulate the activities of the submucosal glands, when the drug is given in higher concentrations. Bromhexine markedly dissolves AGP in granules of the secretory cells.

Animals↗
PubMed1981

Clearance by voluntary coughing and its relationship to subjective assessment and effect of intravenous bromhexine.

The elimination of 6 micrometers radioactively tagged teflon particles by 1-2 min of voluntary coughing was studied by profile scanning in 12 patients with tracheobronchial hypersecretion. The patients were tested on 2 different days 40-50 min after receiving 8 mg bromhexine (4 mg in two patients) and placebo intravenously according to a double blind cross-over design. Bromhexine did not influence the elimination of test particles in the nine patients in whom the measurements were technically satisfactory. When asked to identify the day they received bromhexine, the patients failed to do so. However, eight of the nine patients, in whom clearance measurements could be performed, believed they had received bromhexine on the day when most particles were eliminated (P less than 0.01), which coincided with the day on which coughing was easiest. It is suggested that self-assessment of the efficacy of coughing might be a simple, yet reliable technique for studying the short-term influence of drugs on tracheobronchial clearance by coughing.

Adult↗
PubMedDate not supplied

Assessment of bromhexine as a treatment regimen in Sjögren's syndrome-like disease in the NOD (non-obese diabetic) mouse.

OBJECTIVE: Bromhexine has been reported to alleviate the xerostomia and xerophthalmia associated with secondary Sjögren's syndrome. The aim of this study was to determine if it might prove useful in the treatment of Sjögren's syndrome-like disease of the NOD mouse model for autoimmune sialoadenitis. METHODS: Groups of mice were divided into sets receiving 60 mg/kg bromhexine in drinking water and control pair-fed animals. The efficacy of drug treatment was assessed by weekly measurement of stimulated saliva volumes, protein concentration, and amylase activity. At termination (20 weeks) submandibular and lacrimal glands were removed to assess the levels of lymphocytic infiltration by histological evaluation under light microscopy. RESULTS: Control and bromhexine-treated groups of mice showed no difference in the loss or rate of reduction in stimulated saliva flow over the 12 weeks of treatment. No differences were noted in the protein concentration and amylase loss with increasing age of the animals. Similar temporal changes in total protein profiles and aberrant expression of the 20 kDa parotid secretory protein isoform were observed by SDS-polyacrylamide gel profiles and Western bolt analysis. Histological evaluation of exocrine gland sections failed to detect any reduction in focal lymphocyte infiltration. CONCLUSION: Bromhexine therapy did not alter the development or severity of Sjögren's syndrome-like disease in the NOD mouse model for autoimmune sialoadenitis.

Amylases↗
PubMed1980

Selected ion monitoring assay for bromhexine in biological fluids.

A method has been developed for quantification of bromhexine in plasma using gas chromatography mass spectrometry with selected ion monitoring. A deuterium labelled analogue was synthesized and used as the internal standard. To evaluate the gas chromatographic electron capture detection method described earlier, 23 plasma samples have been analysed by both techniques. Although a good correlation was shown, selected ion monitoring was superior to the electron capture detection method for levels below 3 ng ml-1. The mass spectrometric method has also been used to set up a pharmacokinetic study of bromhexine in horses. Urine extracts were subjected to gas chromatographic mass spectrometric analysis to identify the different metabolites of bromhexine. Three groups of metabolites were detected and identified.

Animals↗
PubMed1985

Effect of bromhexine, ambroxol, and placebo on clinical and histopathological changes in "Sjögren" mice.

Hybrids of New Zealand black and New Zealand white mice were used in an animal model for Sjögren's syndrome. The animals were treated with bromhexine (Bisolvon), ambroxol (Mucosolvan), or placebo from their 20th week of life for 10-17 weeks. The parotic glands were examined in a masked fashion by light and transmission electron microscopy after treatment. Significant inhibition of pathological changes in the parotic glands was observed by both methods in hybrids receiving 60 mg/kg bromhexine. Other types of treatment had no effect. In addition, the animals receiving the high dosage of bromhexine had a significantly higher survival rate than other hybrids.

Ambroxol↗
PubMed1996

The antioxidative activity of the mucoregulatory agents: ambroxol, bromhexine and N-acetyl-L-cysteine. A pulse radiolysis study.

Ambroxol and bromhexine are shown to be scavengers of both superoxide and hydroxyl radicals as determined by pulse radiolysis experiments. The dismutation of superoxide was accelerated 3-fold by bromhexine and 2.5-fold by ambroxol over the rate of spontaneous dismutation. The reaction constants of hydroxyl radicals with bromhexine and ambroxol were determined by competition kinetics to be 1.58 +/- 0.15 x 10(10) M-1S-1 and 1.04 +/- 0.1 x 10(10) M-1S-1, respectively. N-acetyl-L-cysteine also reacted with hydroxyl radicals (1.28 +/- 0.14 x 10(10) M-1S-1) but not with superoxide radical. These effects may be clinically relevant in the treatment of oxidant-associated lung damage induced by inflammatory agents and/or environmental pollutants.

Acetylcysteine↗
PubMed1995

Flow-injection extraction-spectrophotometric determination of bromhexine with orange IV.

An automatic flow-injection photometric method for the determination of bromhexine is proposed. The drug was determined by formation of an ion-pair with orange IV, extraction into 1,2-dichloroethane and measurement of the absorbance at 412 nm of the organic phase. A linear calibration graph was obtained at concentrations of 5 x 10(-6)-1.6 x 10(-4) M of bromhexine. Up to 40 samples h-1 can be processed with an RSD of 0.32-0.88%. The method was applied to the determination of bromhexine in blood serum and a pharmaceutical preparation.

Azo Compounds↗
PubMed2000

Determination of the minor component bromhexine in cotrimoxazole-containing tablets by absorption spectrophotometry and partial least-squares (PLS-1) multivariate calibration.

The mucolitic bromhexine [N-(2-amino-3,5-dibromobenzyl)-N-methylcyclohexylamine] has been determined in cotrimoxazole-containing tablets by partial least-squares (PLS-1) multivariate of spectrophotometric calibration data in the spectral range 310-350 nm. In the studied commercial tablets, cotrimoxazole is present in large excess (ca. 100:1 in weight) with respect to bromhexine, and a high degree of spectral overlapping exists among bromhexine and cotrimoxazole components. However, the obtained recoveries are reasonably good with the presently discussed technique.

Bromhexine↗
PubMed1987

Nebulization treatment with saline compared to bromhexine in treating chronic sinusitis in asthmatic children.

Twenty children aged 3 to 14 years with a history of bronchial asthma complicated by chronic sinusitis were studied in a double-blind study. Patients received, at random, over a period of 2 weeks, either 2 ml saline or 2 ml bromhexine (2 mg/ml) t.i.d. by means of a home nebulizer. A significant decline of clinical symptoms during both nebulization treatments as compared to the pretreatment symptom score was observed (mean score of 1.5 +/- 0.7 and 0.5 +/- 0.8, respectively, P less than 0.01). Both types of nebulization were equally efficient in reducing the symptom score. Radiological abnormalities were significantly more reversed after saline nebulization as compared with bromhexine (P less than 0.05), although both treatments showed radiological improvement (P less than 0.01). The present study indicates that nebulization with saline may have some beneficial effect on chronic sinusitis in asthmatic children. Bromhexine was not superior to saline for this purpose.

Adolescent↗
PubMed1991

Role of bromhexine in exacerbations of bronchiectasis. Double-blind randomized multicenter study versus placebo.

The effectiveness of bromhexine in the treatment of patients with bronchiectasis, in a stage of clinical exacerbation, was assessed in a double-blind, placebo-controlled trial involving 88 in-patients. Bronchiectasis was diagnosed by bronchography and/or CT scan. Bromhexine or matched placebo was administered as 30-mg capsules three times daily per os. Ceftazidine, 1 g i.m., was given to all patients once a day for the first week only. Bromhexine seemed to improve the clinical picture, with significantly positive trends for expectoration, quantity of sputum and auscultatory findings. It also increased the FEV1 and was well-tolerated. Both patients and investigators judged it efficacious.

Adult↗