Sirolimus PK trial: a pharmacokinetic study of the sirolimus-eluting Bx velocity stent in patients with de novo coronary lesions.

This 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.