The pharmacokinetics of acitretin and its 13-cis-metabolite in psoriatic patients.
The synthetic retinoic acid derivative acitretin has recently been introduced for the treatment of severe psoriasis. Hitherto, the use of the carboxylic acid ester analogue, etretinate, has been hampered by an extremely long elimination half-life of up to 120 days for this drug. In the presented study, 12 patients with severe psoriasis were treated with 30 mg acitretin daily for a period of 6 months. The maximum plasma concentration of the drug occurred within about 0.9 to 4.6 hours with an apparent absorption half-life ranging from 0.2 to 1.7 hours and with half-lives of the distribution phase within the range of 1.2 to 3.5 hours. After stopping therapy, the terminal elimination half-life of acitretin varied between 16.5 and 111.1 hours (mean: 47.1 hr +/- 29.8 SD), whereas that for the 13-cis-metabolite varied between 36.5 and 249.4 hours (mean: 119.4 hr +/- 73.4 SD). Suction blister fluid concentrations of both the parent drug and metabolite were lower than plasma concentrations. The mean concentration of serum triglycerides was significantly elevated during the course of therapy, but still remained within the normal range. Saliva concentrations of drug and metabolite at steady-state were below 1 ng/mL. It is not possible from the observed half-lives of acitretin and its 13-cis-metabolite to draw any definite conclusion with regard to the anticonceptional period after acitretin therapy in psoriatic patients.
Larsen
F G
FG
Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark.
Jakobsen
P
P
Eriksen
H
H
Grønhøj
J
J
Kragballe
K
K
Nielsen-Kudsk
F
F
D017255:Acitretin; D000328:Adult; D001768:Blister / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism*; D012463:Saliva / Q000737:chemistry; D014212:Tretinoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D014212:Tretinoin; D017255:Acitretin