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)
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Department of Biologia Animale, University of Modena, Italy.
Volpi
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Palmieri
L
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Bahous
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I
Ronca
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G
D000328:Adult; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004187:Disaccharides / Q000032:analysis; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010003:Osteoarthritis / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects
D004187:Disaccharides; D002809:Chondroitin Sulfates