Adaxil Mechanism of Action

Pharmaco-therapeutic Group: Product for the treatment of osteoarthritis.
Pharmacology: ADAXIL is a medicinal product containing the active ingredients glucosamine sulphate and chondroitin sulphate.
Glucosamine sulphate: The active ingredient glucosamine sulphate is the salt of an amino-monosaccharide glucosamine which is physiologically present in the human body and used, together with sulphates, for the biosynthesis of hyaluronic acid of the synovial fluid and of glycosaminoglycans of the fundamental substance of articular cartilage.
The mechanism of action of glucosamine sulphate is therefore the stimulation of glycosaminoglycans synthesis and thus of the articular proteoglycans. Moreover, glucosamine has anti-inflammatory activities and inhibits the degradation processes of articular cartilages, thus supporting from one side the activity on osteoarthritis symptoms, and from the other side the possible delay of the articular structural damage evidenced in the long-term clinical studies.
Short- and medium-term clinical studies have shown that the efficacy of glucosamine sulphate on osteoarthritis symptoms is evident already after 2-3 weeks from the beginning of administration. On the other hand, the symptomatic efficacy of glucosamine sulphate treatment, versus common analgesics and nonsteroidal anti-inflammatory drugs, is ideal after 6-month continuous cycles, or after 3-month cycles with an evident residual effect of 2 months after withdrawal.
Clinical studies of daily continuous treatment up to 3 years have shown a decrease on osteoarthritis symptoms and a delay, radiologically determined, of structural damage at joint level.
Chondroitin sulphate: Chondroitin sulphate is an important component of most vertebrate tissues. It is predominantly present in the extracellular matrix surrounding cells and is most abundant in those tissues with a large extracellular matrix such as those that form the connective tissues of the body, cartilage, skin, blood vessels and also bone, ligaments and tendons.
Chondroitin sulphate has anti-inflammatory activity and affects cartilage metabolism. In fact, Chondroitin sulphate is an inhibitor of extracellular proteases involved in the metabolism of connective tissues. The addition of chondroitin sulphate to the medium of a chondrocytes culture from human articular cartilage resulted in an increase of proteoglycans concentration of the pericellular matrix and a dose-dependent decrease in collagenolytic activity.
Oral administration of chondroitin sulphate has shown to stimulate proteoglycan production of chondrocytes; to inhibit the production of certain proteolytic enzymes.
Short and long-term clinical trials have demonstrated that chondroitin sulphate is effective in relieving symptoms of osteoarthritis.
Glucosamine and Chondroitin sulphate combination: Glucosamine and chondroitin sulphate synergistically act to stimulate glycosaminoglycan synthesis. Combining these substances produces, from one site, the upregulation of the synthetic activities in chondrocytes and, from the other site, the inhibition of degradative enzymes.
When combined in an animal osteoarthritis model, glucosamine and chondroitin sulphate were more effective than the compounds alone.
Clinical studies in animals and man have further indicated that the combination therapy is effective and allows a significant drop in NSAIDs use by osteoarthritis patients.
Analgesics and NSAIDs may be used concomitantly with ADAXIL, either for rescue analgesia during possible flares of the disease, or in the initial period of treatment, when the symptomatic effects of the product may be delayed for few weeks. Physical therapy programs can be used concomitantly with ADAXIL in the overall management of osteoarthritis.
Pharmacokinetics: Glucosamine: Animal and human studies, carried out with ¹⁴C-labelled glucosamine, have shown that after oral administration, glucosamine is rapidly and almost completely absorbed at systemic level (about 90% of the radioactive dose is absorbed). The steady-state concentrations of glucosamine in plasma and in the synovial fluid after repeated once-a-day doses of 1500 mg are in the range of 10 μM and therefore in line with those which have shown a pharmacological activity in in vitro experimental models, which justify the mechanism of action and the clinical effect of the drug.
After oral absorption, glucosamine is significantly distributed in extravascular compartments (including synovial fluid) with an apparent distribution volume of 37-fold higher than the total human body water quantity. In humans, glucosamine has shown to have affinity for joint tissues. In man, the terminal elimination half-life of glucosamine from plasma has been estimated as around 15 h. Experimental results show that the kidneys significantly contributes to the elimination of glucosamine and/or of its metabolites.
Chondroitin sulphate: The bioavailability after oral administration is 15-24%. A 10% of absorbed chondroitin sulfate appears in unmetabolized form and 90% as depolymerized derivatives with lower molecular weight, as a result of first-pass effect metabolism.
Distribution volume of chondroitin sulfate is relatively low. In humans, chondroitin sulfate has shown to have affinity for joint tissues.
At least 90% of chondroitin sulphate dose is first metabolized by lysosomal sulphateses, and after that it is depolymerized by hyaluronidases, i.e. β-glucuronidases and β-N-acetyl hexose amidases. Liver, kidneys and other organs are involved in the depolymerization of chondroitin sulphate.
On overage, chondroitin sulphate remains in the body 5-15 hours. Main part of chondroitin sulphate and its depolymerized derivatives are eliminated through the kidneys.