PHARMACOKINETICS OF THE NEW ORAL BLOOD GLUCOSE-LOWERING AGENT -(4-TERT-BUTYLPHENOXY)-7-(4-CHLOROPHENYL)-HEPTANIC ACID SODIUM-SALT IN MICE, RATS AND DOGS

The pharmacokinetic behavior of the a-activated carbonic acid (4-tert. -butylphenoxy)-7-(4-chlorophenyl)-heptanic acid sodium salt ((-)-BM 13 .1074-Na) was examiend in ob/ob mice, rats and dogs. By applying an en antioselective HPLC-method, the in vivo stability of the administered (-)-enantiomer could be demonstrated in all tested species. After or a l administration the compound was absorbed quickly and maximum plasma levels were reached within 1 h (ob/ob mice and rats) and 3 h (dogs), r espectively. In dose proportionally, studies in ob/ob mice, with close s of 0.25 and 1 mg/kg, a clear non proportional . increase of the plas ma levels was observed. The terminal half-lives of (-)-BM 13.1074 afte r multiple dosing are approx 30 h in ob/ob mice, 9 h in rats and appro x. 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 m g/l in rats and 105.6 mg/l in dogs, respectively.