Absorption, Distribution and Excretion
Following oral administration, carbocysteine is rapidly absorbed from the gastrointestinal tract, reaching peak serum concentrations within 1–1.7 hours. Approximately 30%–60% of the oral dose is excreted unchanged in the urine. Carbocysteine penetrates well into pulmonary and bronchial secretions. Information regarding the clearance rate of carbocysteine in the literature is unclear. Metabolism/Metabolites The metabolic pathway of carbocysteine involves acetylation, decarboxylation, and sulfoxide formation, ultimately producing pharmacologically inactive carbocysteine derivatives. Due to genetic polymorphism in sulfoxide formation capacity, its metabolism varies significantly. Two cytoplasmic enzymes are responsible for the metabolism of carbocysteine: cysteine dioxygenase and phenylalanine 4-hydroxylase. Decreased metabolism leads to increased carbocysteine exposure, which explains the differences in clinical response among patients, who may have polymorphisms affecting the enzymes that metabolize carbocysteine. Sulfonation is generally considered to be the main metabolic pathway of carbocysteine; however, a team of researchers discovered a novel urinary metabolite, S-(carboxymethylthio)-L-cysteine (CMTC). In this study, cysteine sulfoxide metabolites were not detected in the urine of patients taking carbocysteine.

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

Protein Binding
There is no information in the literature regarding the plasma protein binding of carboxymethylcysteine.

[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 with the structure L-cysteine, in which the hydrogen on the thiol group is replaced by a carboxymethyl group. It has expectorant properties. It is an L-cysteine thioether and also a non-protein L-α-amino acid. It is the conjugate acid of S-carboxymethyl-L-cysteine (1-). Dyspnea and cough are common symptoms of chronic obstructive pulmonary disease (COPD) and other respiratory diseases characterized by increased mucus secretion. COPD patients are at higher risk of lung infections because viruses and bacteria grow and accumulate in thick bronchial mucus. Carbocysteine is an expectorant that relieves respiratory symptoms and infections by reducing the viscosity of mucus, making it easier to expel. Several marketing authorizations for the drug have been withdrawn after severe and even fatal paradoxical reactions in children treated with carbocysteine. Doctors in France and Italy have reported symptoms such as dyspnea, shortness of breath, and worsening cough after taking carbocysteine. Currently, carboxymethylcysteine has not been approved by the U.S. Food and Drug Administration (FDA) or Health Canada, but it is approved for use in Asia, Europe, and South America. S-carboxymethyl-L-cysteine is a metabolite of E. coli (K12 strain, MG1655 strain), produced or discovered by E. coli. It is a compound formed by the reaction of iodoacetic acid with sulfhydryl groups in proteins. It has been used as an anti-infective nasal spray with expectorant and antitussive effects. Drug Indications Carboxymethylcysteine is available as an over-the-counter or prescription drug for clearing respiratory secretions associated with increased mucus production. Mechanism of Action Excessive mucus production is characteristic of serious respiratory diseases including asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD). It blocks bacterial adhesion to cells, thereby preventing lung infections. Glycoproteins (fucoprotein, sialic acid mucin, and sulfated mucin) regulate the viscoelasticity of bronchial mucus. The levels of fucoglycoprotein in the mucus of patients with chronic obstructive pulmonary disease (COPD) are elevated. Carboxycysteine may reduce mucus viscosity by stimulating intracellular sialyltransferase to restore the balance between sialic acid mucin and fucoglycoprotein. One study found that L-carboxycysteine can inhibit hydrogen peroxide (H₂O₂)-induced cell damage by activating protein kinase B (Akt) phosphorylation, suggesting that L-carboxycysteine may have antioxidant effects and prevent lung cell apoptosis. Some evidence suggests that L-carboxycysteine can inhibit the NF-κB and ERK1/2 MAPK signaling pathways, thereby reducing TNF-α-induced inflammation in the lungs and other inflammatory pathways. An in vitro study found that L-carboxycysteine can reduce the expression of intercellular adhesion molecule 1 (ICAM-1), thereby inhibiting rhinovirus 14 infection and alleviating airway inflammation.

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Pharmacodynamics
Due to its mucolytic properties, carbocysteine can significantly reduce sputum viscosity, relieving cough, dyspnea, and fatigue. Furthermore, it can reduce respiratory mucus accumulation, thereby preventing lung infections; this is particularly beneficial for preventing acute exacerbations of chronic obstructive pulmonary disease (COPD) caused by bacteria and viruses. In vitro studies have shown that it possesses anti-inflammatory activity and a certain degree of free radical scavenging effect.

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.)