Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate

Chondroitin sulfate (Condrosulf(R)) was characterized for structure, physicochemical properties and purity. This glycosaminoglycan has a relative molecular mass of about 14,000, a sulfate-to-carboxyl ratio of 0,95 due to the high percentage of monosulfated disaccharides (38 % 6-monosulfate and 55 % 4-monosulfate) and a low amount of disulfated disaccharides (1.1 %) inside the polysaccharide chains No other glycosaminoglycans were detected in the preparation. Chondroitin sulfate was labelled by reduction with sodium H-3-borohydride and administered by oral route in the rat and dog. More than 70 % of radioactivity,vas absorbed and found in urine and tissues. The plasma radioactivity was fractionated by size-exclusion chromatography in three fractions: radioactivity associated with high, intermediate and low molecular mass compounds. The peak value of the concentration of high molecular mass radioactivity compounds in plasma was reached after 1.6 and 2.1 h for the rat and dog, respectively After 36 h the high molecular mass radioactivity compounds were still present in plasma of dog and rat. After 24 h radioactivity was higher in the intestine, liver, kidneys, synovial fluid and cartilage than in other tissues Condroitin sulfate was orally administered to man (healthy volunteer) in a single daily close of 0.8 g and in two daily doses of 0.4 g. The results showed that both forms of administration determined a significant increase of plasma concentration of chondroitin sulfate as compared with predose value over a full 24 h period. Elimination constant values and t(max) (of the first administration in the case of fractionated dose) were almost the same for the two administrations. Some biochemical parameters (number of leukocytes, proteins, sulfated glycosaminoglycans and hyaluronic acid amounts, and N-acetylglucosaminidase activity) of synovial fluid were evaluated in controls and treated osteoarthritic subjects. No variations were observed in the patient who did not receive chondroitin sulfate. Five days of chondroitin sulfate administration led to a significant increase of concentration and molecular mass of hyaluronan and a decrease of a lysosomal enzyme N-acetyl-glucosaminidase. No significant differences in leukocyte count and protein content were detected