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

Abstract

BTS 67 582 stimulates insulin release and causes dose-dependent glucose-lowering activity in the conscious beagle dog. Plasma glucose levels were lowered within 1 h and were maximally reduced by 53.2± 2.7% 2–3 h after oral dosing with 90 μmol/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 glucose was calculated as 24.7 μmol/kg. No effect on the urinary excretion of glucose was observed (except for a marginal increase at the highest dose tested, 90 μmol/kg BTS 67 582). Insulin-stimulated glucose disposal is, therefore, 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 sodium excretion by 2.8- and 2.9-fold by BTS 67 582 at 30 and 90 μmol/kg, respectively, without increased potassium excretion. In separate studies, increases in the urinary clearance of both creatinine and p-aminohippuric acid were observed with BTS 67 582 at 90 μmol/kg, indicating that changes in glomerular filtration rate and renal blood flow, respectively, may have contributed to this diuretic effect. BTS 67 582 had no effect on blood pressure or heart rate. In conclusion, in the conscious beagle dog BTS 67 582 stimulates insulin secretion, causes dose-dependent lowering in plasma glucose, and also possesses mild eukalemic diuretic properties. Drug Dev. Res. 47:137–143, 1999. © 1999 Wiley-Liss, Inc.