N Volpi1. 1. Department of Biologia Animale, Biological Chemistry Section, University of Modena and Reggio Emilia, Modena, Italy. volpi@unimo.it
Abstract
OBJECTIVE: Chondroitin sulfate (CS) has proven to be a valuable therapeutic tool as a symptomatic slow-acting drug for the treatment of osteoarthritis after oral administration. The aim of this study was to assess the absorption of CS of ichthyic origin after oral administration to 20 healthy male volunteers. DESIGN: Ichthyic origin CS (from shark cartilage, 4 g) was orally administered to 20 healthy human volunteers, and then extracted and purified from plasma over a 48 h period. The polysaccharide absorbed by oral route was characterized and quantified by agarose-gel electrophoretic technique, and densitometric scanning. In addition, the percentage of constituent disaccharides and charge density were measured. RESULTS: After oral administration, ichthyic CS plasma levels increased (more than 120%) with a peak concentration at 8.7h, with the increase reaching significance from 4 to 16 h. A significant decrease in the relative amount of non-sulfated disaccharide was measured (reaching the minimum relative percentage of 30.86+/-20.79% at 8h). At the same time, 4-sulfated disaccharide increased to a maximum of 51.91+/-25.91% at 6h, and 6-sulfated and disulfated disaccharides appeared in blood, reaching maximum concentrations of 15.24+/-16.60% at 8h and 2.93+/-4.82% at 12h, respectively. Concomitantly, the mean charge density rose from 0.40+/-0.14 at predose to a maximum of 0.72+/-0.22 and 0.72+/-0.21 measured 8 and 12h after ichthyic CS administration. CONCLUSIONS: Ichthyic CS is absorbed slowly, with a t(max)=8.7+/-4.5h and the C(max)averaged 4.87+/-2.05 microg/ml. The differences in the absorption and bioavailability of the various CS formulations is strongly influenced by the structure and characteristics, such as molecular mass, charge density, and cluster of disulfated disaccharides, of the parental molecules.
OBJECTIVE:Chondroitin sulfate (CS) has proven to be a valuable therapeutic tool as a symptomatic slow-acting drug for the treatment of osteoarthritis after oral administration. The aim of this study was to assess the absorption of CS of ichthyic origin after oral administration to 20 healthy male volunteers. DESIGN: Ichthyic origin CS (from shark cartilage, 4 g) was orally administered to 20 healthy human volunteers, and then extracted and purified from plasma over a 48 h period. The polysaccharide absorbed by oral route was characterized and quantified by agarose-gel electrophoretic technique, and densitometric scanning. In addition, the percentage of constituent disaccharides and charge density were measured. RESULTS: After oral administration, ichthyic CS plasma levels increased (more than 120%) with a peak concentration at 8.7h, with the increase reaching significance from 4 to 16 h. A significant decrease in the relative amount of non-sulfated disaccharide was measured (reaching the minimum relative percentage of 30.86+/-20.79% at 8h). At the same time, 4-sulfated disaccharide increased to a maximum of 51.91+/-25.91% at 6h, and 6-sulfated and disulfated disaccharides appeared in blood, reaching maximum concentrations of 15.24+/-16.60% at 8h and 2.93+/-4.82% at 12h, respectively. Concomitantly, the mean charge density rose from 0.40+/-0.14 at predose to a maximum of 0.72+/-0.22 and 0.72+/-0.21 measured 8 and 12h after ichthyic CS administration. CONCLUSIONS: Ichthyic CS is absorbed slowly, with a t(max)=8.7+/-4.5h and the C(max)averaged 4.87+/-2.05 microg/ml. The differences in the absorption and bioavailability of the various CS formulations is strongly influenced by the structure and characteristics, such as molecular mass, charge density, and cluster of disulfated disaccharides, of the parental molecules.