Volpi N
Department of Biologia Animale, Biological Chemistry Section, University of Modena and Reggio Emilia, Italy.
Osteoarthritis Cartilage. 2002 Oct;10(10):768-77. doi: 10.1053/joca.2002.0824.
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) (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.
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.
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 microg/ml. After administration of Condrosulf), chondroitin sulfate plasma levels increased (more than 200%) in all subjects with a peak concentration after 2h, with the increase reaching significance from 2 to 6h. 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 4h). At the same time 4-sulfated disaccharide increased to a maximum of 60.50+/-10.45% after 4h and 6-sulfated disaccharide appeared in blood, reaching a maximum concentration of 17.33+/-6.52% after 2h. Concomitantly the mean charge density increased from 0.40+/-0.09 at pre-dose to a maximum of 0.78+/-0.11 4h after Condrosulf) administration. As for safety, the treatment was well tolerated and did not determine any relevant change in vital signs nor ECG.
From this study and literature data, it appears that exogenous chondroitin sulfate (Condrosulf) is absorbed as a high molecular mass polysaccharide together with derivatives resulting from a partial depolymerization and/or desulfation.
骨关节炎（OA）的药物治疗包括症状性慢作用药物（SYSADOA）。这类化合物起效缓慢，可改善OA症状。在SYSADOA中，康得灵（Condrosulf）（由IBSA生产），其活性成分是硫酸软骨素，经口服后已被证明是治疗OA症状的一种有价值的治疗手段。本研究的目的是评估20名健康男性志愿者口服康得灵后硫酸软骨素及其成分的生物利用度。在给予康得灵后，测定药代动力学参数以及血浆硫酸软骨素的结构和性质。还评估了一天内内源性硫酸软骨素血浆水平可能的生理调节情况。
将康得灵（由牛源性硫酸软骨素组成，4 g）口服给予20名健康人类志愿者，并在48小时内从血浆中提取和纯化硫酸软骨素衍生物。通过琼脂糖凝胶电泳技术和光密度扫描对经口服吸收的多糖组分进行表征和定量。此外，测量组成二糖的百分比和电荷密度，以从物理化学角度表征经口服吸收的硫酸软骨素组分。
所有受试者的内源性硫酸软骨素血浆水平均可检测到，对6名受试者计算的平均值在一天内从0.3至5.3微克/毫升不等。给予康得灵后，所有受试者的硫酸软骨素血浆水平均升高（超过200%），2小时后达到峰值浓度，从2至6小时升高具有显著性。给药后血浆中二糖组成相对于基线的变化也证明了外源性硫酸软骨素的吸收。测量到非硫酸化二糖的相对量显著降低（在4小时达到最低相对百分比22.96±11.68%）。同时，4 - 硫酸化二糖在4小时后增加至最大值60.50±10.45%，6 - 硫酸化二糖出现在血液中，2小时后达到最大浓度17.33±6.52%。同时，平均电荷密度从给药前的0.40±0.09增加至给予康得灵后4小时的最大值0.78±0.11。至于安全性，该治疗耐受性良好，未引起生命体征或心电图的任何相关变化。
从本研究和文献数据来看，外源性硫酸软骨素（康得灵）作为一种高分子量多糖连同部分解聚和/或脱硫产生的衍生物被吸收。
