J Pharm Pharmaceut Sci (www.ualberta.ca/~csps) 5(2):181-184, 2002 181 Single Dose Pharmacokinetics and Bioavailability of Glucosamine in the Rat Ali Aghazadeh-Habashi, Saeed Sattari, Franco M. Pasutto and Fakhreddin Jamali Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton AB, T6G 2N8, Canada Received 1 November 2001, Revised 2 May 2002, Accepted 5 June 2002 Abstract Purpose: To study the pharmacokinetics of glu- cosamine following various routes of administration of the hydrochloride salt to rats and to locate the site of its first- pass metabolism. Methods: Rats were cannulated in the jugular vein and single intravenous, oral and intraperitoneal doses of 350 mg.kg -1 were administered. Serial blood sam- ples were collected and plasma glucosamine concentra- tions were determined using HPLC. Results: After intravenous administration, the apparent terminal half-life (1.09 ± 0.98 h), apparent steady state volume of distribu- tion (2.1 ± 1.1 L.kg -1 ) and total body clearance (2.61 ± 0.81 L.kg -1 .h -1 ) were calculated. The peak plasma concen- tration, after oral administration, occurred approximately 30 min post-dose and the absolute bioavailability was 0.19. Glucosamine was completely bioavailable after intraperito- neal administration. Conclusion: Orally administered glu- cosamine is rapidly absorbed, highly distributed and efficiently cleared. The gut rather than liver is mainly responsible for the first pass metabolism since reduced bioavailability is observed after oral but not intraperitoneal doses. INTRODUCTION Osteoarthritis affects approximately 12% of the general population and the incidence increases with age (1). Cur- rent drug therapies, including acetaminophen and nonste- roidal anti-inflammatory drugs, do not slow or reverse the degenerative process in osteoarthritis. Glucosamine (2- amino-2–deoxy-D-glucose) has recently received a great deal of public attention as a treatment for osteoarthritis, prompting scientists to investigate its clinical usefulness and potential adverse effects (1). It has been proposed that glucosamine stops and possibly reverses the degenerative process in osteoarthritis (2). Pharmacokinetic studies of glucosamine in the rat, dog and man have been reported (3-5). However, these investigations have been conducted with radiolabeled drug and do not differentiate between glucosamine and its metabolites and/or degradation prod- ucts. We have applied a recently reported specific and sen- sitive HPLC-UV assay (6) to delineate the glucosamine pharmacokinetics. To explore the site of first pass-metabo- lism of glucosamine we followed the plasma time course of the drug after administration of single doses to rats via the intravenous (i.v.), intraperitoneal (i.p.) and oral (p.o.) routes. MATERIALS AND METHODS Materials D-(+)-glucosamine hydrochloride, D-(+)-galactosamine hydrochloride and 1-naphthyl isothiocyanate (>95%) were purchased from Sigma Chemical Company (St. Louis, MO, USA). Methanol and acetonitrile were purchased from Caledon Laboratory Ltd (Georgetown, ON, Canada) while triethylamine and acetic acid were purchased from BDH Inc. (Toronto, ON, Canada). All chemicals and solvents were ACS analytical or HPLC grade. The styrene divinyl- benzene quaternary ammonium solid-phase cartridges (200mg/4.0 mL; particle size range 45 - 150µ) were obtained from Alltech Associates, Inc (Deerfield, IL, USA). Animals The study protocol was approved by the Health Sciences Animal Policy and Welfare Committee of the University of Alberta. A group of five male Sprague-Dawley rats (260 ± 4g) was used in i.v. and oral crossover studies with a two-day wash- out period between the two doses. The same cannula was used for bolus injection and for withdrawal of blood sam- ples. Following bolus injection, the cannula was washed with normal saline solution to avoid the possibility of carry-over. A different group of six rats, in the same weight range, was used in the i.p. study. Rats were housed in cages and maintained in a controlled environment with free access to food and water. Corresponding Author: F. Jamali, Faculty of Pharmacy & Pharma- ceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8. fjamali@pharmacy.ualberta.ca