The invention pertains to methods and devices for controlling the pharmacokinetics of administered substances, particularly therapeutic substances by combining advantages of delivery to two or more compartments within the skin. The invention provides methods and devices for delivering substances to subcutaneous and intradermal compartments of the skin to achieve a hybrid pharmacokinetic profile that has a portion similar to that achieved by intradermal delivery, e.g., rapid and high peak onset levels of the substance, and a portion similar to that achieved by subcutaneous delivery, e.g., longer circulating levels of the substance.