Pharmacokinetics of some new oral blood glucose-lowering agents in dogs

The determination of the plasma concentrations of the new oral antidiabetic agents BM 17.0505 (2-(4-cyclopentylphenoxy)-7- (4-chlorphenyl)-heptanic acid), BM 13.1196 (2-(4-chlorphenyl)- heptanic acid), BM 13.1196 (2-(4-cyclopentylphenoxy)-7-(2-methoxy- phenyl)-heptanic acid: BM 13.1188 (2-(4-benzylphenoxy)-7-(2-methoxy- phenyl)-heptanic acid) and BM 13.1180 (2-(4-butylphenoxy)-5- (4-chlorphenyl)-pentanic acid) in dog plasma were performed by using liquid-liquid extraction and high-performance liquid chromatography with ultraviolet (220 nm) detection. The analytical procedures have recoveries of more than 90%, and a between-run precision of less than 5% for all analysed compounds. The pharmacokinetic behaviour, especially the dose proportionality, was investigated in dogs after a single oral dose of 5 and 50 mg/kg and repeated oral doses of 5 and 50 mg/kg, respectively. All compounds were absorbed quickly and attained maximum plasma concentrations within 1-3 h after administration. In the examined interval of dosing, a clear non proportional increase of the plasma levels was observed. After repeated oral doses the terminal half-lives are about 60-70 h (BM 17.0505), 80 h (BM 13.1196), 30 h (BM 13.1180) and 100-140 h (BM 13.1180).