PMID: 11902659Mar 21, 2002Paper

30-day intravenous administration of VRCTC-310-ONCO in rabbits

Il Farmaco
N O StanchiL A Costa

Abstract

VRCTC-310-ONCO, an agent based on the snake phospholipase A2 (crotoxin), is currently under clinical development. After phase I study in patients by intramuscular administration, the interest of intravenous (IV) dosing arose. To evaluate IV administration of VRCTC-310-ONCO in rabbits, ten animals were subjected to surgical implant of fixed jugular catheter, by which they received daily IV doses of 0.03 mg/kg body weight of VRCTC-310-ONCO for 30 days (n = 8) or saline (n = 2). The procedure was well tolerated in all rabbits. One of the animals died after the sixth dose of VRCTC-310-ONCO with CNS involvement; two additional rabbits required dose-reduction. All other rabbits achieved 30 days of treatment and were sacrificed. All rabbits (even controls) developed lymphocytosis and mild anaemia, without changes in blood neutrophils. No changes were found in serum transaminases (GOT and GPT), cholesterol, triglycerides, and y-glutamyl transpeptidase. At necropsy, chronic granulation tissue was found surrounding the implant in all rabbits. VRCTC-3 10-ONCO-treated rabbits presented generalised and marked swelling of hepatocytes, with areas of cytoplasmic vacuolisation. No abnormalities were found in kidney, heart, lung, spleen, adrenal...Continue Reading

References

Jan 1, 1986·Journal of Toxicology and Environmental Health·S T WolfordR Ruhren
Oct 1, 1983·Critical Care Medicine·J R HagemanC E Hunt
Feb 1, 1993·Investigational New Drugs·R E CorinM A Etcheverry

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Citations

Apr 1, 2014·BioMed Research International·Leonardo A CalderonAndreimar M Soares

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