Extravasation injury potential of CI-980, a novel synthetic mitotic inhibitor.
Severe soft-tissue ulceration is known to result from inadvertent extravasation of a number of anticancer drugs, including tubulin-binding vinca alkaloids, during intravenous administration. CI-980 is a novel anticancer drug candidate that also inhibits mitosis by binding to tubulin. Intradermal administration of CI-980 to mice at doses of 0.02 and 0.05 mg produced ulcerative lesions in 3/5 and 2/5 animals, respectively, that were significantly smaller than those produced in all animals at vinblastine doses of 0.05 and 0.1 mg. Ulcerative lesions resulting from CI-980 treatment were also less persistent, resolving in 2-8 days versus 7-16 days following vinblastine administration. As based on the common dose of 0.05 mg, CI-980 appears to have significantly less vesicant activity than vinblastine.
MacDonald
J R
JR
Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division of Warner-Lambert Company, Ann Arbor, MI 48105.
Pegg
D G
DG
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects*; D003864:Depression, Chemical; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000209:etiology*; D007271:Injections, Intradermal; D007509:Irritants; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis / Q000187:drug effects; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D012883:Skin Ulcer / Q000139:chemically induced*; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
D000970:Antineoplastic Agents; D002219:Carbamates; D007509:Irritants; D011719:Pyrazines; D011725:Pyridines; D014747:Vinblastine; C072383:canertinib dihydrochloride