Effect of Hyaluronidase and Partially Depolymerized Hyaluronate on Threshold Doses of Drugs.

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Abstract
Atropine sulfate was injected subcutaneously with either hyaluronidase or partially depolymerized hyaluronate (PDHA) to antagonize pilocarpine-induced salivation in rabbits. The minimal effective concentration of a potent local anesthetic was applied with and without hyaluronidase to the rabbit''s cornea to determine its effects on the induction time and duration of anesthesia by the wink reflex. Hyaluronidase and PDHA markedly reduced the interval between time of subcutaneous injection and systemic effects as well as decreasing the minimal effective dose of atropine necessary to antagonize pilocarpine-induced salivation. The shortening of the induction and the lowering of the minimal effective dose by hyaluronidase and PDHA approached those obtained with intravenous atropine. Similarly, 360-1000 TRU of hyaluronidase facilitated penetration of the minimal effective concentration of a local anesthetic applied topically to the cornea and hastened the onset of anesthesia without affecting the duration. Concentrations of hyaluronidase greater than 1000 TRU prevented the development of anesthesia during the observation period.

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