A REVIEW OF NONCLINICAL TOXICOLOGY STUDIES OF BECAPLERMIN (RHPDGF-BB)

Becaplermin (recombinant human platelet-derived growth factor-BB [BB h omodimer, rhPDGF-BB]) has demonstrated a favorable safety profile in a series of nonclinical studies designed to assess its systemic toxicit y, sensitization, local irritation, and genotoxic potential. No signif icant local or systemic toxicity directly attributable to becaplermin was observed following single and multiple intravenous or subcutaneous administration at doses up to 3 mg/kg in monkeys. Administration of s ingle large intravenous doses (up to 100 mg/kg) and repeated dosing at 1 or 3 mg/kg in mice resulted in rapidly reversible vasodilation and central nervous system depression. In a bone-toxicity study, becaplerm in produced histomorphologic changes suggestive of accelerated bone re modeling, which were judged to be potentially reversible. Similar find ings have not been observed in humans. Although becaplermin was not co nsidered a dermal or ocular irritant, some skin-sensitizing effects we re observed in animals; this finding was not unexpected for a recombin ant human-derived protein. Becaplermin was not genotoxic in a variety of in vitro assays and in one in vivo assay. Am J Surg. 1998;176(Suppl 2A):55S-60S. (C) 1998 by Excerpta Medica, Inc.