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).
Heitzmann
T
T
Pharmaceutical-Chemical Institute, University of Heidelberg, Germany.
Neidlein
R
R
Freund
P
P
Reiff
K
K
Strein
K
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D006207:Half-Life; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007202:Indicators and Reagents; D008297:Male; D013056:Spectrophotometry, Ultraviolet
D007004:Hypoglycemic Agents; D007202:Indicators and Reagents