Stereoselective disposition of the geometric isomers of a novel lipoxygenase cyclo-oxygenase inhibitor in dog and photochemical interconversion of its isomers.

ABSTRACT

A sensitive (10 ng/mL) and specific high-performance liquid chromatographic (HPLC) assay, with electrochemical (EC) detection, for the geometric isomers of 3-hydroxy-N-(2-phenyl-2-(2-thienyl)ethenyl-5-(trifluoromethyl)benzo(b) thiophene-2-carboxamide in dog and human plasma has been developed. Both isomers strongly absorb light, leading to an efficient E in equilibrium Z photoisomerization. After iv administration of a single isomer (Z) to a dog, only the Zisomer was detected in plasma; no in vivo conversion to the E isomer was observed. However, when a mixture of the E and Z isomers (58.641.4) was administered in the same manner to the same dog, the EZ ratio decreased significantly to 47.552.5 six hours after drug administration, indicating stereoselective disposition of the isomers. The elimination of the E isomer was found to be faster than that of the Z isomer.