Investigation of the effects of BTS 67 582, a novel antidiabetic agent, inthe beagle dog

BTS 67 582 stimulates insulin release and causes dose-dependent glucose-low ering activity in the conscious beagle dog. Plasma glucose levels were lowe red within 1 h and were maximally reduced by 53.2 +/- 2.7% 2-3 h after oral dosing with 90 mu mol/kg BTS 67 582 (equivalent to 22.5 mg/kg as the free base). A dose of BTS 67 582 causing a 25% (ED25) reduction of plasma glucos e was calculated as 24.7 mu mol/kg. No effect on the urinary excretion of g lucose was observed (except for a marginal increase at the highest dose tes ted, 90 mu mol/kg BTS 67 582). Insulin-stimulated glucose disposal is, ther efore, the most likely cause of the glucose-lowering effect of BTS 67 582. BTS 67 582 significantly increased urine flow by 1.9- and 2.2-fold and sodi um excretion by 2.8- and 2.9-fold by BTS 67 582 at 30 and 90 mu mol/kg, res pectively, without increased potassium excretion. In separate studies, incr eases in the urinary clearance of both creatinine and p-aminohippuric acid were observed with BTS 67 582 at 90 mu mol/kg, indicating that changes in g lomerular filtration rate and renal blood flow respectively, may have contr ibuted to this diuretic effect. BTS 61 582 had no effect on blood pressure or heart rate. In conclusion, in the conscious beagle dog BTS 67 582 stimul ates insulin secretion, causes dose-dependent lowering in plasma glucose, a nd also possesses mild eukalemic diuretic properties. (C) 1999 Wiley-Liss, Inc.