Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Clinical Factors Affecting the Serum Retention of a Teratogenic Etretinate after the Acitretin Administration

  • Jeong, Jong Heon (Department of Dermatology, Dongguk University Ilsan Hospital, School of Medicine) ;
  • Hyun, Gyu Hwan (College of Pharmacy, Seoul National University) ;
  • Park, Yu Jeong (Department of Dermatology, Dongguk University Ilsan Hospital, School of Medicine) ;
  • Kwon, Sung Won (College of Pharmacy, Seoul National University) ;
  • Lee, Ai-Young (Department of Dermatology, Dongguk University Ilsan Hospital, School of Medicine)
  • Received : 2022.05.18
  • Accepted : 2022.07.07
  • Published : 2022.11.01
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Abstract

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.

Keywords

Acknowledgement

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HP20C0131).

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