A method is provided of localizing a drug action where the drug is present throughout a vascular system. The localization occurs to within a volume of blood in a blood vessel, the vascular system having an initial temperature substantially within a first temperature range. A temperature-specific enzyme is delivered throughout a vascular system including a volume of blood in a blood vessel, the temperature-specific enzyme having a working temperature within a prespecified temperature range that does not substantially overlap the first temperature range. A heat transfer element is delivered to a blood vessel in fluid communication with the volume of blood. The temperature of the heat transfer element is adjusted such that the volume of blood in the blood vessel is heated or cooled to the prespecified temperature range. In this way, the action of the temperature-specific enzyme is substantially limited to the volume of blood heated or cooled. In an alternative embodiment, the temperature-specific enzyme is localized to the volume of blood in the blood vessel, and the heat transfer element is disposed in fluid communication with the volume of blood in the blood vessel. The enzyme localization may occur by way of direct injection or by way of injection through a lumen of a catheter. The injection lumen of the catheter may be disposed at least partially adjacent or in combination with the heat transfer element and its associated inlet and outlet lumens.