Glucosamine

Absorption

In a pharmacokinetic study, glucosamine was 88.7% absorption by the gastrointestinal tract. Absolute oral bioavailability was 44%, likely due to the hepatic first-pass effect. In a pharmacokinetic study of 12 healthy adults receiving oral crystalline glucosamine, plasma levels increased up to 30 times the baseline levels and Cmax was 10 microM with a 1,500 mg once-daily dose. Tmax was about 3 hours. AUC was 20,216 ± 5021 after a 15,000 mg dose.

Toxicity

The oral LD50 of glucosamine in rats is >5000 mg/kg. Symptoms of an overdose with glucosamine may include nausea, vomiting, abdominal pain, and diarrhea (common side effects of this drug). Severe and life-threatening hypersensitivity reactions to glucosamine may occur in patients with a shellfish allergy or asthma.

Description

D-Glucosamine is a monosaccharide that contains an amine group in place of one of the hydroxyl groups. Like most saccharides, it exists mostly in a cyclic configuration (the α-form is shown here) rather than as its linear form.
Only the D-enantiomer of glucosamine exists in nature. It is found in chitin (a cellulose-like polymer of N-acetylglucosamine), mucoproteins (proteins with >4% carbohydrate content), and mucopolysaccharides (polysaccharides that contain repeating amino sugar/non-amino sugar disaccharides).
Georg Ledderhose, a medical student at Strasbourg University (then in Germany), isolated glucosamine from cartilage-derived chitin in 1876 and named it glycosamin. Chemist Emil Fischer and his student Hermann Leuchs at the University of Berlin first reported its synthesis in 1902 (the same year that Fischer was awarded the Nobel Prize in Chemistry).
Glucosamine, as its sulfate salt and often in combination with the polydisaccharide chondroitin, is marketed over-the-counter as a treatment for osteoarthritis inflammation and its accompanying pain. Despite numerous clinical trials, however, there is little evidence that it is effective for this or any other malady. As a result, the US Federal Drug Administration has not approved glucosamine for medical use. FDA has sued at least two drug companies for making false claims about their glucosamine products.
By 2003, many European countries had approved glucosamine salts as safe, effective treatments for managing arthritis pain. But in 2009, the European Food Safety Authority (EFSA), responding to a request from the European Commission, stated, “A cause and effect relationship has not been established?between the consumption of glucosamine [salts] . . . and the maintenance of normal joints.”
The report added, “A cause and effect relationship has not been established between the dietary intake of glucosamine [sulfate] and reduction of inflammation in the general population.”

Chemical properties

(β form.) Colorless needles. Mp 110C (decomposes). Very soluble in water; slightly soluble in methanol and ethanol; insoluble in ether and chloroform.

Occurrence

Glucosamine is found in mucopolysaccharides, chitin, and mucoproteins. Glucosamine is a naturally occurring substance; glucosamine sulfate is manufactured synthetically.

The Uses of Glucosamine

Glucosamine is an amino sugar that can regulate growth factor gene transcription. It is also widely touted as remedy for osteoarthritis (OA).

The Uses of Glucosamine

Pharmaceutic aid.

Background

Osteoarthritis (OA) is a progressive and degenerative joint disease marked by loss of cartilage, bone changes, and synovial membrane inflammation. Treatment with chondroprotective drugs, such as glucosamine sulfate may offer additional benefits to nonsteroidal anti-inflammatory drugs treating the painful symptoms of OA. Glucosamine is commonly used over the counter as a treatment for arthritic joint pain, although its acceptance as a medical therapy varies due to contradictory and findings with unclear clinical significance during clinical trials. It is currently not approved as a prescription product by the FDA, but is widely available over the counter.

Indications

Glucosamine is generally used over the counter in the symptomatic treatment of osteoarthritis and joint pain, frequently combined with chondroitin sulfate and/or ibuprofen.

Definition

ChEBI: The open-chain form of D-glucosamine.

brand name

Adaxil;Antatril;Arthryl;Chitosamine;Corti-anartril;Dona 200-s;Dona compositum;Donna 200;Pona;Terramycin;Terrastatom;Tetracyn;Thiocondramine;Viartril.

World Health Organization (WHO)

Glucosamine is found in chitin, mucoproteins and mucopolysaccharides. It is used as a pharmaceutical aid. Glucosamine sulfate has been used in the treatment of rheumatic disorders though it is not widely marketed for this purpose.

Pharmacokinetics

The administration of glucosamine, in theory, provides a building block towards the synthesis of glycosaminoglycans, slowing the progression of osteoarthritis and relieving symptoms of joint pain. Studies to this date examining the efficacy of glucosamine sulfate have been inconclusive. Glycosaminoglycans contribute to joint cartilage elasticity, strength, and flexibility. A systematic review of various studies and guidelines determined that modest improvements were reported for joint pain and function in patients taking glucosamine. A consistent joint space narrowing was observed, but with an unclear clinical significance.

Veterinary Drugs and Treatments

These compounds may be useful in treating osteoarthritis or other painful conditions in domestic animals, but large, well-designed controlled clinical studies proving efficacy were not located. One study in dogs (McCarthy, O’Donovan et al. 2007) showed some positive effect, but this study was not placebo controlled and compared responses versus carprofen. Another placebo-controlled, blinded study in dogs (Moreau, Dupuis et al. 2003), did not demonstrate statistically significant improvement after 60 days of treatment.
These compounds potentially could be of benefit in cats with FLUTD (feline lower urinary tract disease) because of the presence of glycosaminoglycans as part of the protective layer of the urinary tract. Controlled studies have shown some positive effects in some cats, but overall did not appear to make a significant difference.

Metabolism

Glucosamine undergoes metabolism in the liver. Metabolism information for glucosamine is limited in the literature.

Purification Methods

Crystallise the amines from MeOH. The free base has been obtained from the hydrochloride (21.5g, see below) in a mixture of Et3N (15mL) and EtOH (125mL) by shaking for 2days at room temperature, and the solid Et3N.HCl is filtered off and the process repeated with more Et3N (3-4 times) until the 
D-glucosamine (15g) is free from Cl ions. It has m 88o , [] D20 +100o mutarotating to +47.5o (c 1, H2O). When Et2NH is used as base, the 
to 
conversion is complete giving 
D-glucosamine. The pentaacetate is purified by dissolving in CHCl3, treating with charcoal, drying (MgSO4), evaporating the solvent, and adding a little dry Et2O to induce crystallisation. It has m 124-126o, [] D +113o (c 1, CHCl3) after 16hours in a desiccator. [Leaback Biochemical Preparations 10 118 1963.] The N-acetyl derivative, m 203-205o from MeOH/Et2O (dry in vacuum P2O5) has [] D +75o to +41o (c 2, H2O); this derivative can also be purified by dissolving in the minimum volume of H2O to which is added 7-8volumes of EtOH followed by Et2O until turbid and keeping at ~20o to crystallise. Wash the crystals with MeOH then Et2O and dry in vacuo over P2O5. [Horton Biochemical Preparations 11 1 1966.]