Potential role for EASI Mechanism of subcutaneous infusion Subcutaneously administered drugs and infusates must traverse an interstitial matrix to enter the vascular or lymphatic system. The interstitium's resistance to drug permeation can be envisioned as functioning like a three-dimensional filter through which drugs/infusates must pass. There are large molecules such as elastin and collagen inhabiting a matrix of hydrated gel-like glycosaminoglycans and proteoglycans. Among the glycosaminoglycans is hyaluronan, which contributes to the resistance of fluid flow through the interstitium. Though hyaluronan is found in lower concentration than collagen in the skin, it plays a disproportionately large role in resisting fluid movement.3 Hyaluronidase modifies connective tissue permeability via hydrolyzing hyaluronic acid, effecting a cleavage of the glucosaminidic bond between N-acetylglucosamine and glucuronic acid moieties. The cleavage results in a decrease in viscosity of the cellular cement and promotes diffusion of injected fluids, facilitating their absorption. The decrease in viscosity is reversed within 24 hours, due to the rapid inactivation of the hyaluronidase enzyme and also due to the rapid turnover rate of skin hyaluronan.4, 5 So-called "spreading agents," historically derived from animal extracts, have been used clinically to facilitate dispersion and absorption of other drugs for over 50 years.4 The extensive history of spreading agent use was relevant to the FDA review of the new recombinant enzyme. Based in part upon the longtime uses of (nonrecombinant) hyaluronidase, the FDA approval for Hylenex states the drug is: "Indicated as an adjuvant to increase the absorption and dispersion of other injected drugs, for hypodermoclysis, and as an adjunct in subcutaneous urography for improving resorption of radiopaque agents." Subcutaneous infusion instead of, or prior to, IV infusion