Chondroitin sulfate

Chondroitin sulfate belongs to the polysaccharide subgroup of glycosaminoglycans.

Chondroitin sulfate is one of the main elements of the cartilage, which joins a central protein, forming what we know as proteoglycan, which is what gives the cartilage its mechanical and elastic properties.

The therapeutic effect of chondroitin sulfate in patients suffering from arthritis, is due to an anti-inflammatory activity at the level of the cellular components of the inflammation (in vivo), to the stimulation of the synthesis of endogen proteoglycans (in vitro) and hyaluronic acid (in vivo), and to a decrease in the catabolic activity of chondrocytes (in vivo), inhibiting some proteolytic enzymes (collagenase, elastase, proteoglycanase, phospholipase A₂, N-acetylglucosaminidase, etc.) (in vitro, in vivo) and the formation of other substances that damage the cartilage (in vitro).

Absorption

Several studies indicate that the bioavailability of chondroitin sulfate fluctuates between 15 and 24% of the dose by oral administration. 10% of the absorbed portion of chondroitin sulfate appears in the form of chondroitin sulfate and 90% in the form of depolymerase derivatives of inferior molecular weight, which suggests that it goes through a first pass effect. After oral administration of chondroitin sulfate, maximum blood levels are reached in about 4 hours.

Distribution

In the blood, 85% of the concentration of chondroitin sulfate and the depolymerase derivatives is bound to plasma proteins. The volume of distribution of chondroitin sulfate is relatively small, around 0.3 l/kg. In humans, chondroitin sulfate shows an affinity for joint tissue. In rats, as well as joint tissue, chondroitin sulfate shows an affinity for the wall of the small intestine, liver, brain and kidneys.

Metabolism

At least 90% of the dose of chondroitin sulfate is metabolised firstly by lysosomal sulfatases, and then is depolymerased by hyaluronidases, beta-glucuronidases and beta-N-acetylhexosaminidases. The liver, the kidneys and other organs take part in the depolymerisation of chondroitin sulfate. There have been no observation interactions with other medicines at metabolisation level. Chondroitin sulfate is not metabolised by cytochrome enzyme P450.

Elimination

The systematic clearance of chondroitin sulfate is 30.5 ml/min or 0.43 ml/min/kg. The average lifetime fluctuates between 5 and 15 hours, depending on the experimental protocol. Elimination of chondroitin sulfate and its depolymerased derivatives is chiefly through the kidneys.

Linearity

The kinetics of chondroitin sulfate are of first order up to single doses of 3,000 mg. Multiple doses of 800 mg in patients suffering from arthritis do not alter the order of the kinetics of chondroitin sulfate.

Toxicity (severe, sub severe and chronic), mutagenicity, genotoxicity, carcinogenicity and reproductive toxicity studies, have given negative results in all cases.