This article is dedicated to the memory of Dr Folmer Nielsen-Kudsk.
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The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol
Article first published online: 21 MAY 2009
DOI: 10.1111/j.1365-2133.2009.09241.x
© 2009 The Authors. Journal Compilation © 2009 British Association of Dermatologists
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How to Cite
Grønhøj Larsen, F., Jakobsen, P., Grønhøj Larsen, C., Heidenheim, M., Held, E. and Nielsen-Kudsk, F. (2009), The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol. British Journal of Dermatology, 161: 664–670. doi: 10.1111/j.1365-2133.2009.09241.x
Publication History
- Issue published online: 20 AUG 2009
- Article first published online: 21 MAY 2009
- Accepted for publication 2 April 2009
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Keywords:
- alcohol;
- isotretinoin;
- metabolism
Summary
Background Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4-oxo-isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half-life.
Objectives To determine if isotretinoin (13-cis-RA), its main metabolite 4-oxo-isotretinoin (4-oxo-13-cis-RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4-oxo metabolite were determined.
Patients/methods Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self-administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4-oxo-isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse-phase high-performance liquid chromatography.
Results Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4-oxo metabolite or the all-trans compounds was chromatographically detectable in any of the patients’ plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies.
Conclusions The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long-term isotretinoin treatment. After ceasing long-term isotretinoin therapy the recommended period of 1 month for using anticonceptive measures in fertile women seems adequate.