Inability to detect plasma etretinate and acitretin is a poor predictor of the absence of these teratogens in tissue after stopping acitretin treatment.
1. Concentrations of etretinate, acitretin and its main metabolite 13-cis-acitretin were measured in plasma and subcutaneous fat samples from 37 women of childbearing age exposed to acitretin before November 1990. Twenty of the women still used acitretin and 17 had stopped therapy for a period ranging from 1 to 29 months. 2. The prevalences of detectable etretinate concentrations were 45% and 83% in plasma and subcutaneous tissue, respectively, among current acitretin users and 18% and 86% among those who had stopped acitretin therapy. Thus, inability to detect plasma etretinate is a poor predictor of the absence of etretinate in fat. 3. Acitretin and/or etretinate were detectable in fat and in some cases in plasma from women who had ceased acitretin therapy for up to 29 months. 4. We suggest that (cis)-acitretin and etretinate should be monitored in subcutaneous tissue when plasma measurements are negative. The recommended contraception period of 2 years after cessation of acitretin therapy should be reconsidered to avoid the risk of teratogenicity.
Sturkenboom
M C
MC
Department of Pharmaceutical Pharmacology and Clinical Pharmacy, University of Groningen, The Netherlands.
de Jong-Van Den Berg
L T
LT
van Voorst-Vader
P C
PC
Cornel
M C
MC
Stricker
B H
BH
Wesseling
H
H
D017255:Acitretin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005050:Etretinate / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009426:Netherlands; D011358:Product Surveillance, Postmarketing; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D012871:Skin Diseases / Q000188:drug therapy; D013723:Teratogens / Q000378:metabolism; D014018:Tissue Distribution
D013723:Teratogens; D005050:Etretinate; D017255:Acitretin