Pharmacokinetics of the new oral blood glucose-lowering agent (-)-2-(4-tert.-butylphenoxy)-7-(4-chlorophenyl)-heptanic acid sodium salt in mice, rats and dogs.
The pharmacokinetic behavior of the alpha-activated carbonic acid (-)-2-(4-tert.-butylphenoxy)-7-(4-chlorophenyl)-heptanic acid sodium salt ((-)-BM 13.1074-Na) was examined in ob/ob mice, rats and dogs. By applying an enantioselective HPLC-method, the in vivo stability of the administered (-)-enantiomer could be demonstrated in all tested species. After oral administration the compound was absorbed quickly and maximum plasma levels were reached within 1 h (ob/ob mice and rats) and 3 h (dogs), respectively. In dose proportionally studies in ob/ob mice, with doses of 0.25 and 1 mg/kg, a clear non proportional-increase of the plasma levels was observed. The terminal half-lives of (-)-BM 13.1074 after multiple dosing are approx. 30 h in ob/ob mice, 9 h in rats and approx. 380 h in dogs. The average effective plasma concentration in ob/ob mice is found to be 43.5 mg/l; minimal toxic concentrations are 58.8 mg/l in rats and 105.6 mg/l in dogs, respectively.
Heitzmann
T
T
Pharmaceutical-Chemical Institute, University of Heidelberg, Germany.
Neidlein
R
R
Freund
P
P
Strein
K
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D006207:Half-Life; D006538:Heptanoic Acids / Q000097:blood / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011917:Rats, Inbred Lew; D013045:Species Specificity; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D006538:Heptanoic Acids; D007004:Hypoglycemic Agents; C083311:2-(4-tert-butylphenoxy)-7-(4-chlorophenyl)heptanoic acid