Sirolimus PK trial: A pharmacokinetic study of the sirolimus‐eluting Bx Velocity stent in patients with de novo coronary lesions

AbstractThis study was conducted to assess the systemic drug release and distribution of sirolimus‐eluting stents. Early results with sirolimus‐eluting stents have demonstrated a favorable outcome for reducing restenosis post coronary intervention. However, the clinical systemic pharmacokinetics of sirolimus released from these stents has not been investigated. Sirolimus‐eluting stents (150–178 mcg/18 mm stent) were implanted in 19 patients with coronary artery disease using standard techniques. Blood samples were obtained at multiple times to determine the kinetics of sirolimus release and elimination. Non‐compartmental analysis showed that the maximum blood concentration of sirolimus occurred between 3 and 4 hr after implantation, with a peak concentration of 0.57 ± 0.12 ng/mL (mean ± SD) and 1.05 ± 0.39 ng/mL in patients receiving one or two stents, respectively. Terminal‐phase elimination half‐life was independent of the number of stents and averaged at 213 hr, a value longer than that seen in patients following oral dosing. The apparent clearance was 1.46 ± 0.45 L/hr with an apparent volume of distribution in the terminal phase of 407 ± 111 L (data for both stent doses pooled). Minimal measurable blood levels were detectable at 7 days. Peak whole blood level following sirolimus stent implantation in humans is proportional to the number of stents implanted. The prolonged terminal half‐life may reflect kinetics of blood clearance combined with continued drug elution and secondary local tissue release. © 2005 Wiley‐Liss, Inc.