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Negligible Systemic Absorption of Topical Isotretinoin Cream: Implications for Teratogenicity
Author(s) -
Chen Chao,
Jensen Bradford K.,
Mistry Goutam,
Wyss Ronald,
Zultak Maurice,
Patel Indravadan H.,
Rakhit Ashok K.
Publication year - 1997
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1997.tb04303.x
Subject(s) - isotretinoin , medicine , absorption (acoustics) , dermatology , pharmacology , acne , materials science , composite material
The objective of the study was to assess the extent of systemic exposure of retinoic acid metabolites after excessive application of 0.1% isotretinoin cream in patients with photodamaged skin. This was a single‐center, open‐label, noncomparative, multiple‐dose study of isotretinoin cream. Eighteen female patients with photodamaged skin received a 10 g topical application of isotretinoin cream once daily to a surface area of ∼2,300 cm 2 for 42 days. The patients were not allowed to have high vitamin A—containing foods, vitamin A supplements, or concomitant medications during the entire study period. Plasma levels of four retinoic acids (isotretinoin, tretinoin, 4‐oxo‐isotretinoin, and 4‐oxo‐tretinoin) were evaluated after 42 days of isotretinoin application and compared with baseline (pretreatment) levels. The mean area under the curve (AUC) in plasma increased by 48% (± SE 9.2) and 77% (± 13) from the 24‐hour pretreatment baseline level for isotretinoin and 4‐oxo‐isotretinoin, respectively, after treatment with excessive amounts of isotretinoin cream, suggesting systemic absorption of isotretinoin cream. This increase in systemic exposure of retinoic acids was less than that reported earlier after the U.S. recommended daily allowance of 5,000 IU of vitamin A supplementation (isotretinoin 141 ± 19% and 4‐oxo‐isotretinoin 171 ± 27%). The minimal systemic availability of isotretinoin cream compared with the U.S. recommended daily allowance for vitamin A supplements provides reasonable evidence for lack of its potential teratogenic risk.