Absorption, Distribution and Excretion
Carbocisteine is rapidly absorbed in the gastrointestinal tract when taken orally with peak serum concentrations achieved within 1 to 1.7 hours.
About 30% to 60% of an orally administered dose is detected unchanged in the urine.
Carbocisteine penetrates well into the lung and bronchial secretions.
Clearance information for carbocisteine is not readily available in the literature.

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Metabolism / Metabolites
Metabolic pathways for carbocisteine include acetylation, decarboxylation, and sulfoxidation, leading to the formation of pharmacologically inactive carbocisteine derivatives. Significant variability exists in metabolism due to genetic polymorphism in sulfoxidation capacity. Two cytosolic enzymes are responsible for the metabolism of carbocisteine: cysteine dioxygenase and phenylalanine 4-hydroxylase. Reduced metabolism can cause increased exposure to carbocisteine, explaining variable clinical response between patients who may polymorphisms affecting the enzymes responsible for carbocisteine metabolism. It is generally accepted that sulfodixation is the main metabolic pathway of carbocisteine, however, one group of researchers found a novel urinary metabolite, S-(carboxymethylthio)-L-cysteine (CMTC). No cysteinyl sulfoxide metabolites were found in the urine of patients taking carbocisteine in this study.

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Biological Half-Life
The plasma half-life of carbicostine is 1.33 hours.

Protein Binding
Plasma protein binding information for carbocisteine is not readily available in the literature.

[1]. Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine. Respir Res. 2019 May 27;20(1):104.

S-carboxymethyl-L-cysteine is an L-cysteine thioether that is L-cysteine in which the hydrogen of the thiol group has been replaced by a carboxymethyl group. It has a role as a mucolytic. It is a L-cysteine thioether and a non-proteinogenic L-alpha-amino acid. It is a conjugate acid of a S-carboxylatomethyl-L-cysteine(1-).
Dyspnea and cough are common symptoms of chronic obstructive pulmonary disease (COPD) and other respiratory conditions characterized by increased mucus production. Individuals with COPD have a greater risk of pulmonary infection due to the growth and accumulation of viruses and bacteria in thick bronchial mucus. Carbocisteine is a mucolytic drug that alleviates respiratory symptoms and infections by reducing the viscosity of mucus, allowing it to be expelled. Several licenses for this drug were withdrawn following serious and fatal paradoxical effects after carbocisteine therapy in children; respiratory dress, dyspnea, and cough aggravation were reported by physicians in France and Italy. Carbocisteine is currently not FDA or Health Canada approved, but is approved for use in Asia, Europe, and South America.
S-Carboxymethyl-L-cysteine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
A compound formed when iodoacetic acid reacts with sulfhydryl groups in proteins. It has been used as an anti-infective nasal spray with mucolytic and expectorant action.

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Drug Indication
Carbocisteine is indicated over the counter and in prescription formulas to clear airway secretions in conditions associated with increased mucus.

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Mechanism of Action
The hypersecretion of mucus characterizes serious respiratory conditions including asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD). It blocks bacterial adherence to cells, preventing pulmonary infections. Glycoproteins (fucomucins, sialomucins and sulfomucins) regulate the viscoelastic properties of bronchial mucus. Increased fucomucins can be found in the mucus of patients with COPD. Carbocisteine serves to restore equilibrium between sialomucins and fucomucins, likely by intracellular stimulation of sialyl transferase enzyme, thus reducing mucus viscosity. A study found that L-carbocisteine can inhibit damage to cells by hydrogen peroxide (H2O2) by activating protein kinase B (Akt) phosphorylation, suggesting that carbocisteine may have antioxidant effects and prevent apoptosis of lung cells. There is some evidence that carbocisteine suppresses NF-κB and ERK1/2 MAPK signalling pathways, reducing TNF-alpha induced inflammation in the lungs, as well as other inflammatory pathways. An in-vitro study found that L-carbocisteine reduces intracellular adhesion molecule 1 (ICAM-1), inhibiting rhinovirus 14 infection, thereby reducing airway inflammation.

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Pharmacodynamics
Due to its mucolytic effects, carbocisteine significantly reduces sputum viscosity, cough, dyspnea and fatigue. Additionally, it prevents pulmonary infections by decreasing accumulated mucus in the respiratory tract; this is especially beneficial in preventing exacerbations of COPD caused by bacteria and viruses. It has in-vitro anti-inflammatory activity with some demonstrated action against free radicals.

C5H9NO4S

179.19

179.025

638-23-3

(RS)-Carbocisteine;25390-17-4

193653

White to off-white solid powder

1.5±0.1 g/cm3

417.3±45.0 °C at 760 mmHg

208-213 °C (dec.)

206.2±28.7 °C

0.0±2.1 mmHg at 25°C

1.588

0.32

3

6

5

11

161

1

C([C@@H](C(=O)O)N)SCC(=O)O

GBFLZEXEOZUWRN-VKHMYHEASA-N

InChI=1S/C5H9NO4S/c6-3(5(9)10)1-11-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/t3-/m0/s1

(2R)-2-amino-3-(carboxymethylsulfanyl)propanoic acid

Mucofan; DF 1794Y; Carbocysteine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~6 mg/mL (~33.48 mM)

Solubility in Formulation 1: 2 mg/mL (11.16 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)