Ronca G, Conte A
Institute of Biological Chemistry, University of Pisa, Italy.
Int J Clin Pharmacol Res. 1993;13 Suppl:27-34.
Chondroitin sulfates and other glycosaminoglycans are administered as drugs to man by intravenous, intramuscular or oral routes. There are some studies on the pharmacokinetics of heparin, heparan sulfate and dermatan sulfate, whereas few data are available on the metabolic fate of chondroitin sulfate in man. Partially depolymerized chondroitin sulfate (mean mol. wt: 7.5 kd, range 5-10 kd) with a ratio of 1:3 between chondroitin-4-sulfate and chondroitin-6-sulfate has been administered as single administrations of 0.2 and 1.2 g by intramuscular and oral routes respectively to 10 healthy volunteers (5 males and 5 females), aging 25-53 years. After intramuscular administration the plasma level increased to a concentration peak at 90 min. The peak concentration, the elimination half-life and the apparent distribution volume were respectively 3.8 mcg/ml, 275 min and 0.40 ml/g. About 37% of the administered chondroitin sulfate is excreted in the urine during the first 24 h as high- and low-molecular-weight derivatives. After oral administration the concentration peak was observed at 240 min. The concentration at the peak, the elimination half-life and the apparent distribution volume were respectively 4.6 mcg/ml, 310 min and 0.44 ml/g. A peak of mono-, oligo- and polysaccharides with a molecular weight lower than 5 kd derived from partial digestion of exogenous chondroitin sulfate is also present in plasma. This study shows that about 10% and 20% of the orally administered drug is absorbed as high- and low-molecular-weight derivatives respectively. Comparison with the results obtained in experimental animals indicate that the metabolic fate of partially depolymerized chondroitin sulfate is similar in man and in experimental animals.
硫酸软骨素和其他糖胺聚糖通过静脉、肌肉或口服途径作为药物施用于人体。关于肝素、硫酸乙酰肝素和硫酸皮肤素的药代动力学已有一些研究，而关于硫酸软骨素在人体中的代谢命运的数据却很少。将硫酸软骨素 -4- 硫酸酯与硫酸软骨素 -6- 硫酸酯比例为 1:3 的部分解聚硫酸软骨素（平均分子量：7.5kd，范围 5-10kd）分别通过肌肉注射和口服途径，以 0.2g 和 1.2g 的单次剂量施用于 10 名年龄在 25 - 53 岁的健康志愿者（5 名男性和 5 名女性）。肌肉注射后，血浆水平在 90 分钟时升至浓度峰值。峰值浓度、消除半衰期和表观分布容积分别为 3.8mcg/ml、275 分钟和 0.40ml/g。在最初的 24 小时内，约 37% 的施用硫酸软骨素以高分子量和低分子量衍生物的形式随尿液排出。口服给药后，在 240 分钟时观察到浓度峰值。峰值浓度、消除半衰期和表观分布容积分别为 4.6mcg/ml、310 分钟和 0.44ml/g。血浆中还存在一个由外源性硫酸软骨素部分消化产生的分子量低于 5kd 的单糖、寡糖和多糖峰。这项研究表明，口服给药的药物分别约有 10% 和 20% 以高分子量和低分子量衍生物的形式被吸收。与在实验动物中获得的结果比较表明，部分解聚硫酸软骨素在人体和实验动物中的代谢命运相似。
