Antidote studies of vinorelbine-induced skin ulceration in the mouse.
The new cantharanthine-modified vinca alkaloid vinorelbine (Navelbine) was administered intradermally (ID) to dehaired BALB/c mice. Dose-dependent skin lesions were produced over the range 0.01-0.5 mg/mouse, with complete healing after 9-35 days. Local (ID) injections of hydrocortisone and saline were ineffective at blocking vinorelbine-induced skin ulceration. Topical skin heating to 43 degrees C or cooling to 10 degrees C were also ineffective. In contrast, hyaluronidase, 15 Units ID, following vinorelbine significantly reduced skin lesions. These results show that vinorelbine is a vesicant and that inadvertent extravasations may be managed with subcutaneous injection of the spreading factor enzyme, hyaluronidase.
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College of Medicine, Pharmacology Department, University of Arizona, Tucson, USA.
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D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006821:Hyaluronoglucosaminidase / Q000627:therapeutic use; D006854:Hydrocortisone / Q000627:therapeutic use; D006979:Hyperthermia, Induced; D007036:Hypothermia, Induced; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D012883:Skin Ulcer / Q000139:chemically induced* / Q000517:prevention & control; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D014747:Vinblastine; D006821:Hyaluronoglucosaminidase; D000077235:Vinorelbine; D006854:Hydrocortisone