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Glucosamine sulfate is a drug used for the treatment of osteoarthritis (OA), based on its pharmacological and metabolic activities on the cartilage and chondrocytes, complemented by mild anti-inflammatory properties and a favorable pharmacokinetic profile. The aim of this study was to define the activity and safety of glucosamine sulfate on the symptoms of patients with OA, using a multicenter, randomized, placebo-controlled, double-blind, parallel-group study design. The study included 252 outpatients with OA of the knee (Lequesne's criteria), radiological stage between I and III, and Lequesne's severity index of at least 4 points and symptoms for at least 6 months. Patients were treated with either placebo or oral glucosamine sulfate 500 mg t.i.d. for 4 weeks, with weekly, with weekly clinic visits. Responders to treatment were defined as patients with a reduction of at least 3 points in the Lequesne's index with a positive overall assessment by the investigator. The Lequesne's index was 10.6 +/- 0.45 S.E.M. points in both groups at the start of the study. This decreased to 7.45 +/- 0.5 points in the treatment group (average 3.2) and 8.4 +/- 0.4 points in the placebo group (average 2.2) (P < 0.05, Student's t-test). The responder rate in the evaluable patients was 55% with glucosamine (N = 120) vs 38% with placebo (N = 121). These proportions were 52% vs 37% in an intention-to-treat analysis (P = 0.014 and 0.016, respectively; Fisher's Exact Test). The medications were well tolerated throughout the study, with no difference between the glucosamine and placebo treated groups. It is concluded that glucosamine sulfate may be a safe and effective symptomatic Slow Acting Drug for OA.

Berberine (BERB) and a combination (COMB) of berberine (CAS 2086-83-1) with policosanol (CAS 557-61-9), red yeast extract (containing monacolin, CAS 557-61-9), folic acid and astaxanthin were orally administered daily for 4 weeks to 40 subjects with moderate dyslipidemias divided in two parallel groups each of 20 subjects. Total cholesterol (TC), LDL, HDL, Non HDL, ApoB, ApoA, Lp(a) and triglycerides (TG) were measured before and at the end of treatments. BERB and COMB significantly reduced TC (respectively by 16% and 20%), LDL (by 20% and 25%), ApoB (by 15% and 29%) and TG (by 22% and 26%), and increased HDL (by 6.6% and 5.1%). Adverse events or impairments of liver transaminases or of CPK were not observed. In conclusion, food supplements containing natural products such as berberine, policosanol, red yeast extracts, folic acid and astaxanthin could be a useful support to diet and life style changes to correct dyslipidemias and to reduce cardiovascular risk in subjects with moderate mixed dyslipidemias.

This article reviews the literature related to the absorption, distribution, metabolism and excretion (ADME) of glucosamine (Gl) in man and in animals after administration of crystalline glucosamine sulfate (CGS). Intravenous administration of CGS In man, after single bolus intravenous (i.v.) injection of 1005 mg CGS (628 mg Gl), the parent Gl disappears from plasma with an apparent half life of 1.11 h. Investigations with uniformly 14C labeled Gl (14C-Gl) administered with 502 mg CGS indicate that the disappearance of Gl is due to an incorporation into the plasma globulins that occurs with a lag time of 0.45 h and a rate of 0.26 h-1. The radioactivity reaches a peak after 10 h and is eliminated with a t1/2 of 95 h. After single i.v. doses of 502 mg CGS traced with 14C-Gl, the urinary excretion in 120 h accounted for 29% of the administered dose. Consistent results are obtained in rat and dogs, in which radioactivity rapidly appears in liver, kidneys and other tissues, including the articular cartilage. In man, after i.v. bolus injection of 1005 mg CGS, the urinary excretion in 24 h of Gl determined with ion exchange chromatography was 38% of the administered dose, mostly in the first 8 h after administration. Similar results were obtained tracing CGS with 14C-Gl. Consistent results of urinary excretion were obtained in rats and dogs tracing CGS with 14C-Gl. The excretion of radioactivity in feces was small. The elimination of radioactivity with the expired air as 14CO2 measured in rats amounted to 49% of the administered dose in the 144 h following the administration, 16% of which occurred in the first 6 h. Intramuscular administration of CGS In man, a single intramuscular injection of 502 mg CGS traced with 14C-Gl, gave results similar to those after i.v. administration. Oral administration of CGS In man, after a single dose of 7.5 g CGS, Gl in plasma was below the limit of quantitation (3 micrograms/ml) of the ion exchange chromatography method. After a single dose of 314 mg CGS traced with 14C-Gl, radioactivity appeared incorporated in plasma globulins with a lag time of 1.5 h and increasing with a rate of 0.24 h-1. The peak was reached at the 9th h after administration. The radioactivity then was eliminated with a t1/2 of 58 h. The absolute oral bioavailability evaluated on the AUCs of the globulin-incorporated radioactivity was 44%. The fecal excretion in 120 h was 11.3% of the administered dose showing that at least 88.7% of the administered dose was absorbed through the gastrointestinal tract. The difference of 45% is probably due to a hepatic first-pass effect. Investigated in the rat with doses from 126 to 3768 mg CGS traced with 14C-Gl, a linear relationship was found with the AUCs as well as between doses and the Cmax of radioactivity in total and in deproteinized plasma. The urinary elimination in man of the parent Gl in 24 h determined with ion exchange chromatography after a single dose of 7.5 g of CGS was 1.19% of the administered dose, occurring mostly in the first 8 h after administration. After...

The present study was designed (a) to characterize the activity of loxiglumide as a peripheral cholecystokinin (CCK) antagonist in healthy human subjects, and (b) to determine whether CCK is a physiologic regulator of the intestinal phase of mealstimulated exocrine pancreatic and biliary secretions in man. Intravenous loxiglumide (22 &mol/kg per h) was highly potent in antagonizing CCK8-induced pancreatic enzyme and bile acid secretion as well as pancreatic polypeptide release. The potency, and selectivity of loxiglumide as an antagonist of CCK provides the tool for evaluating the role of CCK as a physiological mediator of meal-induced pancreatic and biliary'responses in humans. Infusion of a' liquid test meal into the duodenum evoked an immediate response of pancreatic enzyme and bilirubin outputs, respectively. Intravenous loxigiumide significantly inhibited the meal-induced pancreatic amylase output by 63% (P < 0.05), lipase output by 43% (P < 0.05), and bilirubin output by 59% (P < 0.05). These data suggest that CCK is a physiological mediator of the intestinal phase of meal-stimulated pancreatic' and biliary responses. (J. Clin. Invest. 1990. 85:640-646.) CCK antagonist -pancreas