An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of etretinate with the advantage of a much shorter half-life when compared with etretinate. [PubChem]
Indication
For the treatment of severe psoriasis in adults.
Pharmacology
Acitretin is a retinoid. Retinoids have a structure similar to vitamin A and are involved in the normal growth of skin cells. Acitretin works by inhibiting the excessive cell growth and keratinisation (process by which skin cells become thickened due to the deposition of a protein within them) seen in psoriasis. It therefore reduces the thickening of the skin, plaque formation and scaling.
Toxicity
Oral, rat: LD50 = >4000 mg/kg. Symptoms of overdose include headache and vertigo.
Affected Organisms
Humans and other mammals
Biotransformation
Following oral absorption, acitretin undergoes extensive metabolism and interconversion by simple isomerization to its 13-cis form (cis-acitretin). Both parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates, which are excreted.
Absorption
Oral absorption of acitretin is optimal when given with food, and is linear and proportional with increasing doses from 25 to 100 mg. Approximately 72% (range 47% to 109%) of the administered dose was absorbed after a single 50 mg dose of acitretin was given to 12 healthy subjects.
Half Life
49 hours (range 33 to 96 hours)
Protein Binding
Over 99.9% bound to plasma proteins, primarily albumin.
Elimination
Both parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates, which are excreted. The chain-shortened metabolites and conjugates of acitretin and cis-acitretin are ultimately excreted in the feces (34% to 54%) and urine (16% to 53%).
