DOSE PROPORTIONALITY STUDIES OF NOVEL THIAZOLIDINEDIONE DERIVATIVES AS POTENT ANTIDIABETIC AGENTS IN MICE

The determination of the plasma concentrations of the new oral antidia betic agents BM 13.1246 4-oxazolyl)-ethoxy]benzyl]-2,4-thiazolidinedio ne), BM 13.1215 nyl-4-oxazolyl)-methyl-2-benzofuranyl-5-methyl]-2, 4-o xazolidinedione), and BM 50.1050 enyl-4-oxazolyl)-ethoxy]naphthalyl]me thylmethyl-2, 4-thiazolidinedione) in ob/ob mice plasma was performed by using liquid-liquid extraction and high-performance liquid chromato graphy with ultra-violet (270 nm) detection. The analytical procedures have recoveries of more than 80%, and a between-run precision of less than 4% for all analysed compounds. The pharmacokinetic behaviour, es pecially the dose proportionality, was investigated in ob/ob mice afte r repeated oral doses of 1 and 10 mg/kg, respectively. All compounds w ere absorbed quickly and attained maximum plasma concentrations within 2-5 h after administration. In the examined interval of dosing, an ap proximately proportional increase of the plasma levels for BM 13.1246 and BM 50.1050 was observed. After repeated oral doses the terminal ha lf-lives are about 4 h for BM 13.1246, 8 h for BM 13.1215, and 6 h for BM 50.1050.