INTRODUCTION
Acitretin is a second-generation aromatic retinoid. It is
an active metabolite of the precursor drug, etretinate
(Tegison, Hoffmann-La Roche, Nutley, NJ), which was
widely used in the United States (U.S.) as a systemic psoriasis
therapy until 1998 when it was withdrawn from the market
and replaced by acitretin. Etretinate is 50 times more lipophilic
than acitretin and is sequestered in fatty tissues, leading to a
mean terminal half-life of 120 days.1-3 Compared to etretinate,
acitretin has a wider therapeutic index and improved pharmacokinetic
profile. It is relatively water-soluble and has a half-life
of 50 to 60 days. Etretinate and acitretin have nearly identical
therapeutic profiles, with similar levels of efficacy and toxicity.
Acitretin is effective for the treatment of psoriasis and a number
of other keratinizing disorders.4
Acitretin is approved by the U.S. Food and Drug Administration
(FDA) for the treatment of severe recalcitrant psoriasis. It is useful
as monotherapy and has increased efficacy when used in
combination with other topical and systemic therapies, as well
as with phototherapy. Acitretin has also been used off-label in
the treatment of severe keratinization disorders and other dermatoses,
but the data are limited.5,6 We reviewed the current literature including the safety and efficacy of acitretin in clinical
trials for the treatment of psoriasis and other disorders of keratinization,
inflammatory disorders and in the chemoprevention
of malignancies.
METHODS
We conducted a PubMed literature search for the term "acitretin"
which yielded 714 results. The results were further limited
to English language, clinical trials in human subjects. The 78
articles returned were evaluated for relevance and 60 were
included in this review (Figure 1). Here, we present clinical
efficacy data for acitretin as a therapy for psoriasis, other keratinization
and inflammatory disorders and the chemoprevention
of malignancy, as well as safety, tolerability, dosing and cost.
RESULTS
Pharmacokinetics
Acitretin is an orally administered therapy with variable absorption,
which increases with high-fat meals. It has a bioavailability
of approximately 60 percent, with 99 percent of the circulating
