Hyaluronidase, intravenous injection

M. de uiiveira, R. Carbaiio, and H. A. Zimmetman. intravenous injection of hyaluronidase in acute myocardial infarction preliminary report of clinical and experimental obsmvatinns. Am- Heart J. 57 712(1959). 

Subcutaneous injections usually have a lower rate of absorption and slower onset of action than intramuscular or intravenous injections. The rate of absorption may be enhanced by infiltration with the enzyme hyaluronidase. Disadvantages of subcutaneous injection are as follows ... 

Other biological assay methods for hyaluronidase which have been proposed are based on the denuding of rat ova (97), on the rise in hematocrit in rats after intravenous injections of large doses of the enzyme (33), on the changes produced in the ocular structure of rabbits (154,170), on the reduction of the sedimentation rate of erythrocytes in blood containing added hyaluronic acid (16), and on the decapsulation of streptococci (42, 103). Only the last method has gained acceptance, probably because of its great sensitivity. 

Subcutaneous injection of hyaluronidase (150 U/mL) may decrease the morbidity associated with intravenous extravasation injuries [126],... 

In humans, contact with LPS may occur not only during a bacterial infection but also via LPS-contaminated medicaments and solutions administrated intravenously (parenteralia). Since the biological effects of LPS may appear even at concentrations of 1 ng per 1 kg of body weight, drugs intended for parenteral use, have to be endotoxin-free , i.e., thoroughly depyrogenated. In fact parenteralia have to comply with LPS threshold limits (in EU , endotoxin unit) regulated by pharmacopoeias. For example, tetracycline hydrochloride may not contain more than 0.5 ELf/mg. Similar limits exist for insulin (0.8 EU/insulin unit), hyaluronidase (2.3 EU/ hyaluronidase unit), the sodium salt ofheparin for injection (0.003 EU/heparin unit). ... 

Hyaluronidase prepared from mammalian (e.g. bull) testes is given for a variety of disorders and to facilitate the absorption of subcutaneously injected solutions (12). When administered intravenously the first injections may be uneventful, but in a later stage of treatment the chance of anaphylactic shock increases. A case in which anaphylactic ock developed immediately after the 16th injection has been reported (16 ). In this case intracutaneous administration of 7.5 lU hyaluronidase produced an erythema in 10, and a wheal in 30 minutes. However, skin testing prior to every injection is not feasible. 

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