title: Glucosamine dose/concentration-effect correlation in the rat with adjuvant arthritis.
abstract: There is a debate on the dose dependency, concentration-effect, hence, the beneficial effect of glucosamine (GlcN), a widely used anti-inflammatory natural product. We investigated dose/concentration-effect relationship and determined its minimum effective dose/concentration in rats with adjuvant arthritis (AA, Mycobacterium butyricum in squalene) both as preventive and ameliorating interventions. To control already emerged arthritis, rats received oral doses of placebo or 160 mg/kg.day(-1) GlcN for 6 days. For prevention, rats were orally administered 0, 20, 40, 80, or 160 mg/kg.day(-1) GlcN commencing on the day of adjuvant injection. The arthritis index (AI), serum nitrite, and body weight were recorded. Subsequently, animals were cannulated in the right jugular veins and blood samples were collected for the determination of GlcN. GlcN ameliorated and, dose-dependently, prevented AA. It also controlled nitrite. AI was inversely correlated with GlcN dose, maximum plasma concentration, and the area under the concentration curve. Minimum effective dose was approximately 40 mg/kg.day(-1) that correspond to maximum plasma concentration of 1.37 ± 0.24 mg/L, close to 1.6 mg/L reported for pharmaceutical grades of GlcN to humans. GlcN efficacy is dose and concentration dependent. If the data extrapolated to humans, a higher than the commonly tested 1500 mg/kg dosage regimen may provide more clear treatment outcomes.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Aghazadeh-Habashi
authors.forename: M H Gilzad
authors.initials: MH
authors.lastname: Kohan
authors.forename: Waheed
authors.initials: W
authors.lastname: Asghar
authors.forename: Fakhreddin
authors.initials: F
authors.lastname: Jamali
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005944:Glucosamine / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007596:Joints / Q000473:pathology; D008297:Male; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D005944:Glucosamine
keywords: adjuvant arthritis; dose-effect correlation; drug effects; minimum effective dose; pharmacokinetics; rat