Experimental model of doxorubicin extravasation in the mouse

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 dose-related increments in peak toxicity levels, total toxicity, and the duration of damage for each parameter (0.5 > 0.05 > 0.005 mg). Subcutaneous (i.e., 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 - 1980

Fingerprint

Doxorubicin
Toxicity
Theoretical Models
Skin
Intradermal Injections
Erythema
Animals
Intravenous Injections
Antineoplastic Agents
Hydrocortisone
Animal Models
Injections
Tissue

ASJC Scopus subject areas

  • Pharmacology

Cite this

Experimental model of doxorubicin extravasation in the mouse. / Dorr, Robert T; Alberts, David S; Chen, H. S G.

In: Journal of Pharmacological Methods, Vol. 4, No. 3, 1980, p. 237-250.

Research output: Contribution to journalArticle

@article{5b2f4f88e7054805a15993967720ae7b,
title = "Experimental model of doxorubicin extravasation in the mouse",
abstract = "Doxorubicin (Adriamycin{\circledR}), 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 dose-related increments in peak toxicity levels, total toxicity, and the duration of damage for each parameter (0.5 > 0.05 > 0.005 mg). Subcutaneous (i.e., 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.",
author = "Dorr, {Robert T} and Alberts, {David S} and Chen, {H. S G}",
year = "1980",
doi = "10.1016/0160-5402(80)90016-9",
language = "English (US)",
volume = "4",
pages = "237--250",
journal = "Journal of Pharmacological and Toxicological Methods",
issn = "1056-8719",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Experimental model of doxorubicin extravasation in the mouse

AU - Dorr, Robert T

AU - Alberts, David S

AU - Chen, H. S G

PY - 1980

Y1 - 1980

N2 - 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 dose-related increments in peak toxicity levels, total toxicity, and the duration of damage for each parameter (0.5 > 0.05 > 0.005 mg). Subcutaneous (i.e., 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.

AB - 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 dose-related increments in peak toxicity levels, total toxicity, and the duration of damage for each parameter (0.5 > 0.05 > 0.005 mg). Subcutaneous (i.e., 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.

UR - http://www.scopus.com/inward/record.url?scp=0019128724&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019128724&partnerID=8YFLogxK

U2 - 10.1016/0160-5402(80)90016-9

DO - 10.1016/0160-5402(80)90016-9

M3 - Article

VL - 4

SP - 237

EP - 250

JO - Journal of Pharmacological and Toxicological Methods

JF - Journal of Pharmacological and Toxicological Methods

SN - 1056-8719

IS - 3

ER -