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The comparative pharmacokinetics of an anionic cyclopentapeptide endothelin antagonist, BQ-123 (cyclo[d-ASP-PRO-d-VAL-LEU-d-TRP]), was studied using rats and guinea pigs. The compound was determined in the biomaterials including plasma, urine and tissues using a microbore high-performance liquid chromatography system with fluorescence detection. In in vivo i.v. kinetic study, the biliary excretion of BQ-123 was extensive in both rats and guinea pigs, where 70-80% of dose was recovered into bile within 1 hour. Elimination half-life was less than 15 min and total body clearance(CLt) was 50-60 ㎖/min/㎏, similarly in both species. Hepatic metabolism was negligible. In in vitro binding assay using hepatocyte membrane, the nonlinearity of binding was confirmed in both rats and guinea pigs. Overall these elimination kinetic data may suggest that guinea pig has also an effective hepatobiliary transport system like rats. When we consider that the main contributor for the extensive hepatic clearance of BQ-123 is canalicular multispecific organic anion transporter (cMOAT) in rats, it may be that guinea pig has the active transport system for hepatobiliary transport of the peptide.
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