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A Case of Drug-induced Cutaneous Toxicity Observed in Cynomolgus Monkeys

Rie Kikkawa1

  • 1Novartis Institutes for BioMedical Research, East Hanover, New Jersey, USA rie.kikkawa@novartis.com.

Toxicologic Pathology
|May 26, 2016
PubMed

Insights

A novel drug caused skin toxicity in cynomolgus monkeys, presenting as vesicles and scabs. Further investigation is needed to understand the mechanisms of this drug-induced cutaneous toxicity.

Area of Science:

  • Toxicology
  • Dermatology
  • Pharmacology

Background:

  • Drug development requires understanding potential toxicities.
  • Cutaneous toxicity can impact drug safety assessments.
  • Mechanisms of drug-induced skin reactions are not fully understood.

Purpose of the Study:

  • To describe a case of drug-induced cutaneous toxicity in cynomolgus monkeys.
  • To investigate the mechanisms underlying the observed skin lesions.
  • To introduce methods for studying unusual drug toxicities.

Main Methods:

  • Oral administration of a small molecule drug targeting rapidly dividing cells.
  • Clinical and microscopic examination of skin lesions.
  • Immunohistochemical staining to analyze epidermal changes.
  • In-house database searches for differential diagnoses.

Main Results:

  • Multifocal skin lesions, including vesicles and scabs, developed after 7 days of dosing.
  • Lesions were primarily located in thin-skinned areas.
  • Microscopic analysis confirmed epidermal vesicles and ulceration.
  • Immunohistochemistry showed inconsistent levels at the site of epidermal separation.

Conclusions:

  • A novel small molecule drug induced unique cutaneous toxicity in cynomolgus monkeys.
  • The mechanism of epidermal separation appears complex and requires further study.
  • The investigative approach can aid future assessments of drug-induced skin toxicities.
Keywords:
bioinformaticscomputational toxicologycutaneous toxicitycynomolgus monkeysoral gavagesmall moleculevesicle formation

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