Systemic Absorption of Retin-A 0.05%
Systemic absorption of topical tretinoin (Retin-A) 0.05% is negligible, with approximately 2% percutaneous absorption after single or repeated applications, and this minimal absorption does not alter endogenous plasma levels of tretinoin or its metabolites. 1
Quantified Absorption Data
- Percutaneous absorption is approximately 2% after both single-dose application and after 28 days of daily use 1
- With long-term therapy exceeding 1 year, absorption averages only 1.1% 1
- Mean plasma concentrations of tretinoin after 28 days of treatment with 0.05% tretinoin cream showed no significant change compared to endogenous baseline levels 1
Clinical Context for Absorption
The minimal systemic exposure from topical tretinoin is substantially less than that from standard dietary vitamin A intake. When comparing systemic exposure:
- Topical isotretinoin cream (a related retinoid) produced plasma increases of 48% for isotretinoin and 77% for its metabolite after excessive application 2
- This increase was less than the increase from simply taking the U.S. recommended daily allowance of 5,000 IU of vitamin A supplementation (which produced 141% increase in isotretinoin and 171% increase in metabolite) 2
Implications for Special Populations
Pregnant Women
- While no teratogenic effects have been reported with topical tretinoin application, it is not advisable to use during pregnancy or when trying to conceive 3
- The minimal systemic availability compared to dietary vitamin A provides reasonable evidence for lack of teratogenic risk, but caution is still warranted 2
Breastfeeding Women
- The evidence does not specifically address breastfeeding, but given the negligible systemic absorption (1-2%) that does not alter endogenous plasma levels 1, systemic transfer to breast milk would be expected to be minimal
- Vitamin A (retinol) is naturally present in breast milk, and the guidelines recommend breastfeeding mothers receive at least 2.8 mg cyanocobalamin per day orally for general nutrition 4
Key Clinical Takeaway
Neither single-dose nor long-term treatment with topical tretinoin 0.05% formulations affects endogenous levels of tretinoin or its metabolites 1, making systemic effects or toxicity from topical application extremely unlikely when used as directed.