The invention provides a system, device and method for localized application of therapeutic substances within a biological conduit. One embodiment comprises a rotational atherectomy device having a flexible, elongated, rotatable, drive shaft having a lumen and with an eccentric enlarged abrading head having at least one application hole attached therethrough and in communication with a therapeutic agent delivery sheath and an operator-controlled actuator. The therapeutic substances may then spray radially outwardly from the application hole(s) on the eccentric abrading head during and/or after high-speed rotation of the head. Another embodiment comprises compartments in the abrading head that hold therapeutic agent(s) for release during high-speed rotation. In each case, the therapeutic substance(s) is delivered with radial forces resulting from high-speed orbital rotation of the eccentric abrading head, driving the therapeutic substance(s) into the conduit wall.