盐酸氨基葡萄糖和硫酸软骨素在马经口服和静脉单次给药后的生物利用度和药代动力学

The bioavailability and pharmacokinetics of glucosamine hydrochloride and chondroitin sulfate after oral and intravenous single dose administration in the horse.

作者信息

Du Jianping, White Nathaniel, Eddington Natalie D

机构信息

Pharmacokinetics-Biopharmaceutics Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 100 Penn Street, AHB 540C, Baltimore, MD 21201, USA.

出版信息

Biopharm Drug Dispos. 2004 Apr;25(3):109-16. doi: 10.1002/bdd.392.

DOI:10.1002/bdd.392

PMID:15083499

Abstract

OBJECTIVE

The purpose of this study was to determine if glucosamine (GL) hydrochloride (FCHG49) and low molecular weight (LMW) chondroitin sulfate (CS) (TRH122) are absorbed after oral administration to horses. The bioavailability of LMWCS was evaluated by quantifying the total disaccharides found in the plasma following chondroitinase ABC digestion.

METHODS

Two separate studies were conducted. In study 1, ten adult horses received the following four treatments in a randomized crossover fashion: (1) i.v. LMWCS (3 g of 8 kDa), (2) p.o. LMWCS (3 g of 8 kDa), (3) i.v. LMWCS (3 g of 16.9 kDa) and (4) p.o. LMWCS (3 g of 16.9 kDa). Each group received 9 g GL with LMWCS. In a second study, each horse (n=2) was randomly assigned to receive either i.v. administration of GL HCl (9 g) or p.o. administration of GL HCl (125 mg/kg). Blood samples were collected, assayed and pharmacokinetic parameters were determined.

RESULTS

GL was absorbed after oral dosing with a mean C(max) of 10.6 (6.9) microg/ml and a mean T(max) of 2.0 (0.7) h. The extent of absorption of LMWCS after dosing with both the 8.0 and 16.9 kDa provides evidence that LMWCS is absorbed orally. C(max) and AUC were higher (p<0.05) for the 16.9 kDa material compared with 8.0 kDa. However, the 16.9 kDa bioavailability was less than 8.0 kDa, but this difference was not significant.

CONCLUSIONS

This study provides the first report of the bioavailability of orally administered GL and LMWCS in the horse.

摘要

目的

本研究旨在确定氨基葡萄糖（GL）盐酸盐（FCHG49）和低分子量（LMW）硫酸软骨素（CS）（TRH122）经口服给予马匹后是否会被吸收。通过对硫酸软骨素酶ABC消化后血浆中发现的总二糖进行定量，评估LMWCS的生物利用度。

方法

进行了两项独立研究。在研究1中，10匹成年马以随机交叉方式接受以下四种处理：（1）静脉注射LMWCS（3 g 8 kDa），（2）口服LMWCS（3 g 8 kDa），（3）静脉注射LMWCS（3 g 16.9 kDa）和（4）口服LMWCS（3 g 16.9 kDa）。每组在接受LMWCS的同时给予9 g GL。在第二项研究中，每匹马（n = 2）被随机分配接受静脉注射GL HCl（9 g）或口服GL HCl（125 mg/kg）。采集血样进行检测并确定药代动力学参数。

结果

口服给药后GL被吸收，平均C(max)为10.6（6.9）μg/ml，平均T(max)为2.0（0.7）h。给予8.0 kDa和16.9 kDa的LMWCS后，LMWCS的吸收程度证明其可经口服吸收。与8.0 kDa相比，16.9 kDa物质的C(max)和AUC更高（p<0.05）。然而，16.9 kDa的生物利用度低于8.0 kDa，但这种差异不显著。