Acute toxicity evaluation of proliferol: a dose-escalating, placebo-controlled study in swine.
Prolotherapy is one of the many treatments available for chronic musculoskeletal disorders. A commonly used drug contains dextrose 12.5%, glycerin 12.5%, phenol 1.0%, and lidocaine hydrochloride 0.25% in aqueous solution (recently termed Proliferol). For chronic low back pain, this is injected into lumbosacral ligaments to stimulate connective tissue repair. Despite generally positive clinical results, the toxicity of this drug is not well characterized and was assessed in 48 (24 male, 24 female) Yucatan miniature swine randomly assigned to low (1x), medium (5x), or high (10x) dose or saline placebo. Outcomes included clinical observations, clinical chemistry, hematology, coagulation, urinalysis, toxicokinetics, and full gross and microscopic histopathology after 24 hours or 14 days. Findings attributable to Proliferol after 24 hours included dose-response elevations in alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase, which returned to normal after 14 days. There were no remarkable findings in hematology, coagulation, or urinalysis. Urine concentrations of lidocaine and phenol both peaked after 8 hours. Histopathology findings after 24 hours included hemorrhage, inflammation, necrosis, and vascular changes in the ligaments and adjacent soft tissues at the sites of injection. After 14 days, there was evidence of repair under way, with fibrosis and skeletal muscle regeneration at the injection sites.
Dagenais
Simon
S
CAM Research Institute, 27 Peters Canyon Road, Irvine, CA 92606, USA. simon@camresearch.com
Wooley
James
J
Hite
Mark
M
Green
Robert
R
Mayer
John
J
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000652:urine; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005355:Fibrosis / Q000139:chemically induced; D005947:Glucose / Q000008:administration & dosage / Q000633:toxicity*; D005990:Glycerol / Q000008:administration & dosage / Q000633:toxicity*; D006470:Hemorrhage / Q000139:chemically induced; D007249:Inflammation / Q000139:chemically induced*; D007270:Injections, Intra-Articular; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage / Q000633:toxicity*; D008023:Ligaments, Articular / Q000187:drug effects / Q000473:pathology; D008111:Liver Function Tests; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D009336:Necrosis / Q000139:chemically induced; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology; D019800:Phenol / Q000008:administration & dosage / Q000633:toxicity*; D011897:Random Allocation; D012446:Sacroiliac Joint / Q000473:pathology; D013552:Swine; D013556:Swine, Miniature; D023382:Toxicity Tests, Acute; D014657:Vasculitis / Q000139:chemically induced
D000779:Anesthetics, Local; D004338:Drug Combinations; C542771:Proliferol; D019800:Phenol; D008012:Lidocaine; D005947:Glucose; D005990:Glycerol