Pharmacokinetic sub-study in the SPIRIT III randomized and controlled trial of XIENCE V^® everolimus eluting coronary stent system

Background: Drug-eluting stents (DES) are widely used for treatment of coronary artery disease with benefit of reduced restenosis compared to bare metal stents. The XIENCE V^® Everolimus Eluting Coronary Stent System is a second-generation DES system for better deliverability while maintaining safety and efficacy profiles. The present pharmacokinetic sub-study from the SPIRIT III Randomized and Controlled Trial (RCT) was to evaluate systemic exposure of patients to everolimus and to further demonstrate safety following implantation of XIENCE V^® stents with everolimus doses ranging from 53 to 181 μg. Methods and Results: Drug concentrations in whole blood were determined at multiple time points using a validated analytical method with a limit of quantification of 0.1 ng/mL. Individual C_max ranged from 0.17 to 2.40 ng/mL and occurred between 0.07 and 1.88 hours across all dose levels. Both mean and individual C_max values were below the trough blood concentrations of everolimus (Certican^®) for inhibition of organ transplant rejection. The last time point at which drug concentrations could be quantified ranged from 12 to 168 hours postimplantation in individual patients. In most cases, the blood levels dropped below the limit of quantification after 72 hours. Conclusions: This study confirms that the XIENCE V^® stent causes a limited and systemic exposure to everolimus. The presumed localized and efficient delivery of everolimus to target vessels coupled with limited and transient systemic drug exposure contributes to the safety and effectiveness of the XIENCE V^® EECSS in patients of SPIRIT III RCT for longer than 2 years.