The bioavailability and pharmacokinetics of glucosamine hydrochloride and low molecular weight chondroitin sulfate after single and multiple doses to beagle dogs.
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.


RESULTS
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.


CONCLUSIONS
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.
Adebowale
Abi
A
Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD, USA.
Du
Jianpin
J
Liang
Zhonming
Z
Leslie
James L
JL
Eddington
Natalie D
ND
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004338:Drug Combinations; D005944:Glucosamine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008970:Molecular Weight; D013997:Time Factors
D004338:Drug Combinations; D002809:Chondroitin Sulfates; D005944:Glucosamine