Experimental model of doxorubicin extravasation in the mouse

Robert T. Dorr, David S. Alberts, George Chen Hsiao-Sheng George Chen

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Doxorubicin (Adriamycin®), a widely used antitumor agent, can occasionally cause severe and protracted local tissue damage if inadvertently extravasated during intravenous injection. An animal model was developed in adult BALB/c mice to experimentally duplicate such human skin toxicity. Intradermal (ID) doxorubicin injections of 0.5, 0.05 and 0.005 mg (per 0.05 ml) provided reproducible, dose-related skin lesions, quantitated with daily measurement of perpendicular diameters of induration, erythema, and ulceration. Maximal lesions developed rapidly (within 3–5 days) and slowly resolved over 30–40 days. There were doserelated increments in peak toxicity levels, total toxicity, and the duration of damage for each parameter (0.5 〉 0.05 〉 0.005 mg). Subcutaneous (ie, subpannicular) injections, and ID saline control injections did not cause local skin toxicity. A local intervention with ID hydrocortisone (2.5 mg) substantially reduced erythema and induration, and eliminated ulceration only in animals receiving the lower dose (0.05 mg) doxorubicin challenge (p < 0.05). This direct skin toxicity method is compared to reported animal skin toxicity models, and the intervention results are discussed in reference to current toxicity observations in man.

Original languageEnglish (US)
Pages (from-to)237-250
Number of pages14
JournalJournal of Pharmacological Methods
Volume4
Issue number3
DOIs
StatePublished - Jan 1 1980

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Keywords

  • BALB/c mice
  • Doxorubicin
  • Extravasation
  • Skin Toxicity

ASJC Scopus subject areas

  • Pharmacology

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