Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate.

Chondroitin sulfate (Condrosulf) was characterized for structure, physiochemical 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 3H-borohydride and administered by oral route in the rat and dog. More than 70% of radioactivity was 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 dose 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 tmax (of the first administration in the case of fractionated dose) were almost the same for the two administrations.(ABSTRACT TRUNCATED AT 250 WORDS)