Oral bioavailability of chondroitin sulfate (Condrosulf (R)) and its constituents in healthy male volunteers

Drug treatment of osteoarthritis (OA) includes symptomatic slow-acting drugs (SYSADOA). This class of compounds have a slow onset of action and improve OA symptoms. Among the SYSADOA, Condrosulf(R) (manufactured by IBSA), whose active ingredient is chondroitin sulfate, has proven to be a valuable therapeutic tool for the symptomatic treatment of OA after oral administration. The aim of this study was to assess the bioavailability of chondroitin sulfate and its constituents after oral administration of Condrosulf to 20 healthy male volunteers. Pharmacokinetic parameters and the structure and properties of plasma chondroitin sulfate were determined after administration of Condrosulf. The possible physiological regulation of plasma levels of endogenous chondroitin sulfate during the day was also assessed. Design: Condrosulf (composed of bovine origin chondroitin sulfate, 4 g) was orally administered to 20 healthy human volunteers, and chondroitin sulfate derivatives were extracted and purified from plasma over a 48 h period. Polysaccharide fractions absorbed by oral route were characterized and quantified by agarose-gel electrophoretic technique, and densitometric scanning. In addition, the percentage of constituent disaccharides and charge density were measured in an effort to physico-chemically characterize chondroitin sulfate fractions absorbed per os. Results: Plasma levels of endogenous chondroitin sulfate were detectable in all subjects, and the mean values calculated on six subjects varied during the day from 0.3 to 5.3 mug/ml. After administration of Condrosulf, chondroitin sulfate plasma levels increased (more than 200%) in all subjects with a peak concentration after 2 h, with the increase reaching significance from 2 to 6 h. Absorption of exogenous chondroitin sulfate was also proved by the change in the composition of disaccharides in plasma after drug administration with respect to baseline. A significant decrease in the relative amount of non-sulfated disaccharide was measured (reaching the minimum relative percentage of 22.96 +/- 11.68% at 4 h). At the same time 4-sulfated disaccharide increased to a maximum of 60.50 +/- 10.45% after 4 h and 6-sulfated disaccharide appeared in blood, reaching a maximum concentration of 17.33 +/- 6.52% after 2 h. Concomitantly the mean charge density increased from 0.40 +/- 0.09 at pre-dose to a maximum of 0.78 +/- 0.11 4 h after Condrosulf administration. As for safety, the treatment was well tolerated and did not determine any relevant change in vital signs nor ECG. Conclusions: From this study and literature data, it appears that exogenous chondroitin sulfate (Condrosulf(R)) is absorbed as a high molecular mass polysaccharide together with derivatives resulting from a partial depolymerization and/or desulfation. (C) 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.