COMPOSITIONS AND METHODS FOR MODULATING THE PHARMACOKINETICS AND PHARMACODYNAMICS OF INSULIN

摘要

Compositions and methods for modulating the pharmacokinetics and pharmacodynamics of rapid acting injectable insulin formulations are described herein. In the preferred embodiment, the formulations are administered via subcutaneous injection. The formulations contain insulin in combination with a zinc chelator such as ethylenediaminetetraacetic acid ("EDTA") and a dissolution/stabilization agent, and optionally additional excipients. Calcium disodium EDTA is less likely to remove calcium from the body, and typically has less pain on injection in the subcutaneous tissue. Modulating the type and quantity of EDTA can change the insulin absorption profile. Increasing the quantity of citrate can further enhance absorption and chemically stabilize the formulation. In the preferred embodiment, the formulation contains human insulin, calcium disodium EDTA and a dissolution/stabilization agent such as citric acid or sodium citrate. These formulations are rapidly absorbed into the blood stream when administered by subcutaneous injection.