The invention provides a system, device and method for localized application of therapeutic agents within a biological conduit. A preferred biological conduit comprises a blood vessel. A preferred device comprises a high-speed rotational atherectomy device having, in various embodiments, a flexible, elongate non-rotatable therapeutic agent delivery sheath having a lumen therethrough and a flexible, elongated, rotatable, drive shaft with at least one flexible eccentric enlarged abrading head disposed within lumen of the delivery sheath. The operator may actuate a controlled amount or dose of one or more therapeutic agents to release from the distal end of the delivery sheath lumen during high-speed rotation of the drive shaft. The therapeutic agent(s) is thus released into a turbulent fluidic environment resulting from high-speed rotation and orbital motion of the eccentric abrading head, which aids to drivingly urge the therapeutic agent(s) radially through the boundary layer of fluid flow in the conduit and into the target region of the conduit wall.