| Autor: |
Anatomy, Biology, Cell, College, Jefferson Medical, Philadelphia, Laboratories, Argus Research, Pathology, From the Department of, Kochhar, D.M., Christian, M.S. |
| Zdroj: |
Journal of the American Academy of Dermatology; March 1997, Vol. 36 Issue: 3 pS47-S59, 13p |
| Abstrakt: |
Tretinoin has been thoroughly evaluated for its potential as an embryofetal developmental toxicant. Oral tretinoin produces developmental anomalies in animal models; the minimal teratogenic dose is consistently 2.5 to 10 mg/kg. In contrast, topical application does not induce developmental malformations in laboratory animals. A structurally related compound, isotretinoin, is a potent toxicant in humans and animals; the lowest systemic dose that induces fetal anomalies varies more than 100-fold depending on the model. Oral isotretinoin is a more potent developmental toxicant than oral tretinoin in monkeys. Between-drug differences in the metabolism and transplacental transfer of the two retinoids account for the differences in toxicant potency. Pharmacokinetic studies reveal that absorption of tretinoin from the skin is poor and yields maternal plasma concentrations below the developmentally toxic threshold established after oral administration. Analysis of outcomes of developmental toxicology and pharmacokinetic studies suggests that the human risk of fetal anomalies is negligible after therapeutic application of topical tretinoin. (J Am Acad Dermatol 1997;36:S47-S59.) |
| Databáze: |
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