The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol
| Autor: | Folmer Nielsen-Kudsk, Preben Jakobsen, F. Grønhøj Larsen, C. Grønhøj Larsen, Michael Heidenheim, E. Held |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Drug Alcohol Drinking media_common.quotation_subject Metabolite Tretinoin Alcohol Dermatology Pharmacology Young Adult chemistry.chemical_compound Pharmacokinetics Surveys and Questionnaires Acne Vulgaris Humans Medicine Ethanol metabolism Isotretinoin skin and connective tissue diseases Chromatography High Pressure Liquid Acne media_common Ethanol business.industry Middle Aged medicine.disease chemistry Rosacea Female Dermatologic Agents business medicine.drug |
| Zdroj: | Larsen, F G, Jakobsen, P, Grønhøj Larsen, C, Heidenheim, M, Held, E & 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, vol. 161, no. 3, pp. 664-70 . https://doi.org/10.1111/j.1365-2133.2009.09241.x |
| DOI: | 10.1111/j.1365-2133.2009.09241.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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