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Related Experiment Videos

Percutaneous retinoid absorption and embryotoxicity.

C C Willhite1, R P Sharma, P V Allen

  • 1Department of Health Services, State of California, Berkeley.

The Journal of Investigative Dermatology
|November 1, 1990
PubMed
Summary
This summary is machine-generated.

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Topical retinoid application showed rapid skin absorption but limited systemic exposure. Skin toxicity, not teratogenicity, was the primary concern, influencing embryo exposure and bioassay interpretation.

Area of Science:

  • Pharmacology
  • Toxicology
  • Developmental Biology

Background:

  • Topical retinoids are used for various skin conditions.
  • Understanding their absorption, distribution, metabolism, and excretion (ADME) is crucial for efficacy and safety.
  • Assessing the risk of teratogenicity from topical application requires careful consideration of systemic exposure.

Purpose of the Study:

  • To investigate the pharmacokinetics and toxicological effects of topical all-trans-retinoic acid and related compounds in hamsters.
  • To compare systemic absorption and teratogenic potential of topical versus oral retinoid administration.
  • To evaluate the role of skin toxicity in limiting systemic retinoid exposure and embryo risk.

Main Methods:

  • Single and multiple topical applications of all-trans-retinoic acid, etretinate, and arotinoid Ro 13-6298 to hamster skin.

Related Experiment Videos

  • Radioactive labeling ([3H2]-all-trans-retinoic acid) to track absorption and elimination.
  • Pharmacokinetic modeling (two-compartment open model) to describe plasma concentrations.
  • Assessment of local skin reactions (erythema, hyperplasia) and systemic teratogenic effects (malformations, embryo death).

    • Main Results:

    • Rapid absorption and dose-dependent elimination of topical all-trans-retinoic acid from hamster skin.
    • Unchanged all-trans-retinoic acid was a minor fraction of circulating radioactivity; prolonged skin absorption contributed to high bioavailability.
    • Topical doses caused local skin toxicity (erythema, hyperplasia) but not significant teratogenicity.
    • Arotinoid Ro 13-6298 caused dose-dependent mucocutaneous toxicity and increased embryo/offspring abnormalities.
    • Skin toxicity limited systemic absorption and embryo exposure, suggesting it's a critical factor in teratogenicity bioassays.

    Conclusions:

    • Skin toxicity is a major determinant of systemic retinoid exposure following topical application.
    • Comparing absorbed systemic doses, rather than applied topical doses, is essential for interpreting retinoid teratogenicity bioassays.
    • Skin toxicity may limit the amount of retinoid reaching the embryo in humans, while in rodents, it could potentially increase penetration under certain conditions.