PHARMACOKINETICS OF SOME NEW ORAL BLOOD GLUCOSE-LOWERING AGENTS IN DOGS

The determination of the plasma concentrations of tire new oral antidi abetic agents BM 17.0505 -(4-cyclopentylphenoxy)-7-(4-chlorphenyl)-hep tanic acid), BM 13.1196 4-cyclopentylphenoxy)-7-(2-methoxyphenyl)-hept anic acid); BM 13.1188 (2-(4-benzylphenoxy)-7-(2-methoxyphenyl)-heptan ic 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) d etection. The analytical procedures have recoveries of more than 90 %; , and a between-run precision of less than 5 % for all analysed compou nds. The pharmacokinetic behaviour; especially the dose proportionalit y, was investigated in dogs after ct single oral close of 5 and 50 mg/ kg and repeated oral doses of 5 and 50 mg/kg, respectively All compoun ds were absorbed quickly and attained maximum plasma concentrations wi thin 1-3 h after administration. In the examined interval of dosing, a clear non proportional increase of the plasma levels was observed. Af ter repeated oral closes the terminal half-lives are about 60-70 h (BM 17.0505), 80 It (BM 13.1196), 30 h? (BM 13.1180) and 100-140 h? (BM 1 3.1180).