OBJECTIVE The purpose of this study was to determine the oral bioavailability and pharmacokinetics of a glucosamine (GL) and the disaccharides of chondroitin sulfate (CS) after single and multiple-dosing of a GL/CS combination (Cosamin, Cosequin). METHODS Male beagle dogs (n = 8, 12 kg) received the following treatments: (1) IV GL (500 mg)/CS (400 mg), (2) p.o. GL (1500 mg)/CS (1200 mg), (3) p.o. GL (2000 mg)/CS (1600 mg), (4) p.o. GL (1500 mg)/CS (1200 mg) QD for days 1-7 and p.o. GL (3000 mg)/CS (2400 mg) from days 8 to 14. Blood samples were collected over 24 h and glucosamine and the disaccharides of chondroitin sulfate were determined. Pharmacokinetic analysis was performed on glucosamine and total chondroitin sulfate disaccharides and parameters were compared across treatments using ANOVA with post hoc analysis. RESULT After the IV administration, glucosamine declined rapidly in a bi-exponential fashion with a mean (+/- S.D.) elimination t(1/2) of 0.52 (0.25) h. GL absorption was relatively fast (C(max) = 8.95 microg/ml, and T(max) 1.5 h after 1500 mg dose) and the mean bioavailability of glucosamine after single dosing was approximately 12%. The extent of absorption of chondroitin sulfate as indicated by the mean C(max) (21.5 microg/ml) and mean AUC (187 microg/ml h) of total disaccharides after dosing (1600 mg) provides evidence that chondroitin sulfate is absorbed orally. The bioavailability of CS ranged from 4.8 to 5.0% after single dosing and 200-278% upon multiple dosing. CONCLUSION The results of this study show that both glucosamine and chondroitin sulfate (measured as total disaccharides) are bioavailable after oral dosing. In addition, the low molecular weight chondroitin sulfate used in this study displays significant accumulation upon multiple dosing.

中文翻译：

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一次或多次向比格犬给药后，盐酸氨基葡萄糖和低分子量硫酸软骨素的生物利用度和药代动力学。

目的本研究的目的是确定单次或多次服用GL / CS组合（Cosamin，Cosequin）后，葡萄糖胺（GL）和硫酸软骨素（CS）的二糖的口服生物利用度和药代动力学。方法雄性比格犬（n = 8，12 kg）接受以下治疗：（1）IV GL（500 mg）/ CS（400 mg），（2）po GL（1500 mg）/ CS（1200 mg），（ 3）po GL（2000 mg）/ CS（1600 mg），（4）po GL（1500 mg）/ CS（1200 mg）QD第1-7天，以及po GL（3000 mg）/ CS（2400 mg）第8至14天，在24小时内收集血样，并测定了葡萄糖胺和硫酸软骨素的二糖。对氨基葡萄糖和总硫酸软骨素二糖进行了药代动力学分析，并使用ANOVA和事后分析比较了各处理之间的参数。结果静脉注射后，葡萄糖胺以双指数方式迅速下降，平均（+/- SD）消除t（1/2）为0.52（0.25）h。GL吸收相对较快（1500 mg剂量后C（max）= 8.95 microg / ml，T（max）1.5 h），单次给药后葡萄糖胺的平均生物利用度约为12％。给药后（1600 mg）总二糖的平均C（max）（21.5 microg / ml）和平均AUC（187 microg / ml h）表示硫酸软骨素的吸收程度提供了硫酸软骨素被口服吸收的证据。单次给药后CS的生物利用度为4.8％至5.0％，多次给药后为200-278％。结论这项研究的结果表明，口服给药后，葡萄糖胺和硫酸软骨素（以总二糖计）均具有生物利用度。此外，