Systemic exposure of everolimus after stent implantation: A pharmacokinetic study

Objectives We evaluated the pharmacokinetics of the eluted everolimus by assessing systemic drug release and distribution of everolimus-eluting stents. Background Drugs eluted by a coronary stent might cause adverse events such as tumors, infections, or noncardiac death. The systemic exposure of the drugs is unknown because there are only limited data about pharmacokinetics of drug-eluting stents in humans. Methods Venous blood samples in a subset of 39 patients were drown just before implantation of the first stent (baseline, 0-minute time point) and at 10 and 30 minutes and 1, 2, 4, 6, 12, 24, 36, 48, 72, 168, and 720 hours (30 days) after completion of implantation of the last stent. Whole blood concentrations of everolimus were determined using a sensitive validated high-performance liquid chromatography mass spectrometry/mass spectrometry method. Results The total dose of everolimus received by the patients ranged from 53 to 588 mu g. The last time point up to which whole blood concentrations could be quantified ranged per patient from 4 to 720 hours after implantation of the last stent. Across all dose levels, individual T-max values ranged from 0.13 and 2.17 hours; individual C-max ranged from 0.14 to 2.79 ng/mL. Conclusion This study confirms the limited exposure to the systemic circulation of the eluted drug with the use of the XIENCE V Everolimus-Eluting Coronary Stent System (Abbott Vascular, Santa Clara, CA). Therefore, a systemic cause of adverse events is unlikely.