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KMID : 0606920220300060562
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Biomolecules & Therapeutics
2022 Volume.30 No. 6 p.562 ~ p.569
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Clinical Factors Affecting the Serum Retention of a Teratogenic Etretinate after the Acitretin Administration
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Jeong Jong-Heon
Hyun Gyu-Hwan
Park Yu-Jeong
Kwon Sung-Won
Lee Ai-Young
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Abstract
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Etretinate, an acitretin metabolite, has a long retention duration in adipose tissues with a teratogenic potential. FDA advises a contraceptive period of at least three years after discontinuing acitretin. However, the effect of accumulated etretinate in adipose tissues on fetus is unknown. Although the teratogenic threshold for serum concentration of etretinate has been presented as higher than 2 ng/mL, that of acitretin is unknown. To examine factors affecting body retention of acitretin and etretinate, effects of acitretin dosage, acitretin-taking duration, elapsed time after stopping acitretin, age, sex, concomitant alcohol consumption, and foods and supplements rich in vitamin A intake on serum concentrations of acitretin and etretinate were analyzed in 14 acitretin-taken patients and 58 controls without taking acitretin or etretinate. Serum concentrations of acitretin, but not etretinate, tended to be inversely related to the discontinuation duration. They were also related to old age. Different from a published result that alcohol consumption could promote the metabolism of acitretin into etretinate, alcohol intake did not affect serum concentrations of etretinate. Unexpectedly, more frequent intake of vitamin A or provitamin A-rich food and supplements was associated with higher serum acitretin, whereas less frequent intake of vitamin A or provitamin A-rich food and supplements was associated with higher serum levels of etretinate in acitretin-taken patients. Despite preliminary data, inter-individual variations in serum retention of etretinate suggest the necessity of further research before applying the same guidelines to everyone to minimize unnecessary contraception.
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KEYWORD
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Acitretin/etretinate, Teratogenicity, Detectable serum concentration, Discontinuation duration, Age, Vitamin A- or provitamin A-rich food and supplements
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