title: Sirolimus PK trial: a pharmacokinetic study of the sirolimus-eluting Bx velocity stent in patients with de novo coronary lesions.
abstract: 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.
authors.affiliation: MCV Hospitals, VCU Health Systems, Richmond, Virginia, USA.
authors.forename: George W
authors.initials: GW
authors.lastname: Vetrovec
authors.forename: David
authors.initials: D
authors.lastname: Rizik
authors.forename: Clark
authors.initials: C
authors.lastname: Williard
authors.forename: David
authors.initials: D
authors.lastname: Snead
authors.forename: Vladimir
authors.initials: V
authors.lastname: Piotrovski
authors.forename: Gregory
authors.initials: G
authors.lastname: Kopia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003327:Coronary Disease / Q000628:therapy*; D005260:Female; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015607:Stents
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus