Local and systemic drug competition in drug-eluting stent tissue deposition properties

The ability of rapamycin and paclitaxel to compete for specific protein binding and general tissue deposition was assessed for both compounds simultaneously and in the presence of other commonly administered cardiac drugs. Drugs classically used to treat standard cardiovascular diseases, such as hypertension and hypercoaguability, displace rapamycin and paclitaxel from general binding sites, possibly decreasing tissue reserve capacity for locally delivered drugs. Paclitaxel and rapamycin do not affect the other's binding to their biologically relevant specific protein targets, but can generally displace each other from tissue at three log order molar excess, decreasing arterials loads by greater than 50%. Local competitive binding therefore should not limit the placement of rapamycin and paclitaxel eluting stents in close proximity.