DISPOSITION OF BRB-I-28 (7-BENZYL-7-AZA-3-THIABICYCLO[3.3.1]NONANE HYDROPERCHLORATE), A NOVEL ANTIARRHYTHMIC AGENT

The aim of this study was to characterise the pharmacokinetic disposition and tissue distribution of BRB-I-28 (7-benzyl-7-aza-3-thiabicyclo[3.3.1]nonane hydroperchlorate) in rats. The pharmacokinetic disposition was studied by collecting blood samples before and at frequent intervals after intracardiac or oral administration of C-14-labelled BRB-I-28. Two-compartment and 1-compartment pharmacokinetic models were used to describe blood concentration-time profiles after intracardiac and oral administration, respectively. After intracardiac administration, the half-life of elimination (t1/2-beta)from blood ranged from 4.66 to 9.91 hours and the apparent volume of distribution (Vd(area)) ranged from 3.131 to 6.239 L/kg. Oral dosing resulted in rapid and extensive absorption (bioavailability +/- 80%). Distribution of radioactivity into heart, kidney, brain, liver, and perirenal fat was measured by sacrificing rats at various time intervals after oral administration of C-14-labelled BRB-I-28. Extensive distribution of radioactivity occurred in highly perfused organs, particularly liver, kidney and heart. However, levels of radioactivity in brain were low.