Acute Toxicity Pilot Evaluation of Proliferol in Rats and Swine

Abstract

Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.5%, and phenol 1.0% in aqueous solution. Despite extensive previous experience with similar drug solutions administered in humans by intraligamentous injection for chronic musculoskeletal conditions for over 50 years, animal toxicity data are unavailable. A pilot study was conducted to assess acute toxic effects prior to undertaking further assessment of this drug. Test animals were four Sprague-Dawley rats and four Yucatan mini-swine. Rats received injections into lumbar paraspinal muscles, whereas swine received injections into lumbosacral ligaments in an attempt to mirror the method of administration in humans. Two doses were studied equivalent to 1x and 5x the typical human dose. Outcomes measured at 24 h and 14 days included clinical observations, clinical chemistry, hematology, urinalysis, local tolerance, and major organ histopathology. In rats and swine, results from clinical chemistry, hematology, and urinalysis were indicative of acute local inflammation. At the high dose, marked (rats) and moderate (swine) short-term above-normal levels in certain liver enzymes were noted. In rats and swine, local tolerance results were indicative of acute local inflammatory changes in the skin, subcutis, and muscle around the injection sites. In rats and swine, major organ histopathology results did not reveal lesions attributable to the drug and clinical observations were within normal limits. In swine, fibroplasia was noted in deeper muscle tissues after 14 days. Injections of Proliferol in lumbar paraspinal muscles in rats and lumbosacral ligaments in swine elicited a modest acute local inflammatory response with no other indications of local or systemic toxicity.