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Mechanism of Action
Hyaluronidase is a dispersion agent, which modifies the permeability of connective tissue through the hydrolysis of hyaluronic acid, a polysaccharide found in the intercellular ground substance of connective tissue, and of certain specialized tissues, such as the umbilical cord and vitreous humor. Hyaluronic acid is also present in the capsules of type A and C hemolytic streptococci. Hyaluronidase hydrolyzes hyaluronic acid by splitting the glucosaminidic bond between C1 of an N-acetylglucosamine moiety and C4 of a glucuronic acid moiety. This temporarily decreases the viscosity of the cellular cement and promotes dispersion of injected fluids or of localized transudates or exudates, thus facilitating their absorption.
Hyaluronidase cleaves glycosidic bonds of hyaluronic acid and, to a variable degree, some other acid mucopolysaccharides of the connective tissue. The activity is measured in vitro by monitoring the decrease in the amount of an insoluble serum albumin-hyaluronic acid complex as the enzyme cleaves the hyaluronic acid component.
In the absence of hyaluronidase, material injected subcutaneously disperses very slowly. Hyaluronidase facilitates dispersion, provided local interstitial pressure is adequate to furnish the necessary mechanical impulse. Such an impulse is normally initiated by injected solutions. The rate and extent of dispersion and absorption is proportionate to the amount of hyaluronidase and the volume of solution.
The reconstitution of the dermal barrier removed by intradermal injection of hyaluronidase (20, 2, 0.2, 0.02, and 0.002 U/mL) to adult humans indicated that at 24 hours the restoration of the barrier is incomplete and inversely related to the dosage of hyaluronidase; at 48 hours, the barrier is completely restored in all treated areas.
Results from an experimental study, in humans, on the influence of hyaluronidase in bone repair support the conclusion that hyaluronidase alone, in the usual clinical dosage, does not deter bone healing.
Knowledge of the mechanisms involved in the disappearance of injected hyaluronidase is limited. It is known, however, that the components in blood of a number of mammalian species bring about the inactivation of hyaluronidase.
Studies have demonstrated that hyaluronidase is antigenic; repeated injections of relatively large amounts of hyaluronidase preparations may result in the formation of neutralizing antibodies.
HYLENEX recombinant (hyaluronidase human injection) facilitated the administration of subcutaneous fluids in pediatric patients with mild to moderate dehydration in an open-label, multicenter, single arm study in fifty-one (51) patients. A subcutaneous injection of 1 mL (150 U) of HYLENEX recombinant (hyaluronidase human injection) was immediately followed by subcutaneous infusion of isotonic fluids in either the mid-anterior thigh or the inter-scapular area of the upper back.
The safety and flow rate of subcutaneously administered Lactated Ringer's (LR) solution with and without HYLENEX recombinant (hyaluronidase human injection) was evaluated in a prospective, randomized, doubleblinded, placebo-controlled, within-subject, single-center study in fifty-four (54) healthy volunteers. The mean HYLENEX recombinant (hyaluronidase human injection) facilitated infusion rate was 464 mL/hr versus 118 mL/hr for the saline control (p < 0.001, paired t-test).
Last reviewed on RxList: 12/29/2009
This monograph has been modified to include the generic and brand name in many instances.
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