The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol

F Grønhøj Larsen; P Jakobsen; C Grønhøj Larsen; M Heidenheim; E Held; F Nielsen-Kudsk; F Grønhøj Larsen; P Jakobsen; Christian Grønhøj Larsen; M Heidenheim; Elizabeth Held; Folmer Nielsen-Kudsk

doi:10.1111/j.1365-2133.2009.09241.x

The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol

F Grønhøj Larsen, P Jakobsen, C Grønhøj Larsen, M Heidenheim, E Held, F Nielsen-Kudsk, F Grønhøj Larsen, P Jakobsen, Christian Grønhøj Larsen, M Heidenheim, Elizabeth Held, Folmer Nielsen-Kudsk

10 Citations (Scopus)

Abstract

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.

Original language	English
Journal	British Journal of Dermatology
Volume	161
Issue number	3
Pages (from-to)	664-70
Number of pages	7
ISSN	0007-0963
DOIs	https://doi.org/10.1111/j.1365-2133.2009.09241.x https://doi.org/10.1111/j.1365-2133.2009.09241.x
Publication status	Published - 1 Sept 2009

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Grønhøj Larsen, F., Jakobsen, P., Grønhøj Larsen, C., Heidenheim, M., Held, E., Nielsen-Kudsk, F., Grønhøj Larsen, F., Jakobsen, P., Larsen, C. G., 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, 161(3), 664-70. https://doi.org/10.1111/j.1365-2133.2009.09241.x, https://doi.org/10.1111/j.1365-2133.2009.09241.x

Grønhøj Larsen, F, Jakobsen, P, Grønhøj Larsen, C, Heidenheim, M, Held, E, Nielsen-Kudsk, F, Grønhøj Larsen, F, Jakobsen, P, Larsen, CG, 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, https://doi.org/10.1111/j.1365-2133.2009.09241.x

@article{9ddb6100747511df928f000ea68e967b,

title = "The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol",

abstract = "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.",

author = "{Gr{\o}nh{\o}j Larsen}, F and P Jakobsen and {Gr{\o}nh{\o}j Larsen}, C and M Heidenheim and E Held and F Nielsen-Kudsk and {Gr{\o}nh{\o}j Larsen}, F and P Jakobsen and Larsen, {Christian Gr{\o}nh{\o}j} and M Heidenheim and Elizabeth Held and Folmer Nielsen-Kudsk",

note = "Keywords: Acne Vulgaris; Adult; Alcohol Drinking; Chromatography, High Pressure Liquid; Dermatologic Agents; Ethanol; Female; Humans; Isotretinoin; Male; Middle Aged; Questionnaires; Rosacea; Tretinoin; Young Adult",

year = "2009",

month = sep,

day = "1",

doi = "10.1111/j.1365-2133.2009.09241.x",

language = "English",

volume = "161",

pages = "664--70",

journal = "British Journal of Dermatology",

issn = "0007-0963",

publisher = "Wiley-Blackwell",

number = "3",

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TY - JOUR

T1 - The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol

AU - Grønhøj Larsen, F

AU - Jakobsen, P

AU - Grønhøj Larsen, C

AU - Heidenheim, M

AU - Held, E

AU - Nielsen-Kudsk, F

AU - Grønhøj Larsen, F

AU - Jakobsen, P

AU - Larsen, Christian Grønhøj

AU - Heidenheim, M

AU - Held, Elizabeth

AU - Nielsen-Kudsk, Folmer

N1 - Keywords: Acne Vulgaris; Adult; Alcohol Drinking; Chromatography, High Pressure Liquid; Dermatologic Agents; Ethanol; Female; Humans; Isotretinoin; Male; Middle Aged; Questionnaires; Rosacea; Tretinoin; Young Adult

PY - 2009/9/1

Y1 - 2009/9/1

N2 - 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.

AB - 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.

U2 - 10.1111/j.1365-2133.2009.09241.x

DO - 10.1111/j.1365-2133.2009.09241.x

M3 - Journal article

C2 - 19563582

SN - 0007-0963

VL - 161

SP - 664

EP - 670

JO - British Journal of Dermatology

JF - British Journal of Dermatology

IS - 3

ER -

The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol

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