Acitretin: A Comprehensive Pharmacological and Clinical Review

1. Introduction to Acitretin

1.1. Overview and Classification

Acitretin is an oral, second-generation, synthetic aromatic retinoid, a class of compounds structurally related to vitamin A. Retinoids are integral to various physiological processes, including the regulation of cellular growth, differentiation, proliferation, and immune responses.[1] Acitretin is the principal active metabolite of etretinate, a first-generation retinoid. The development of acitretin was driven by the aim to provide a therapeutic agent with a more favorable pharmacokinetic profile than etretinate, specifically a shorter elimination half-life, which was anticipated to reduce the duration of teratogenic risk.[2] This intended pharmacokinetic advantage, however, is notably complicated by in vivo metabolic interactions, particularly the re-esterification to etretinate in the presence of alcohol, which extends its teratogenic potential.[3]

Acitretin is primarily indicated for the systemic treatment of severe, recalcitrant psoriasis and other severe disorders of keratinization that have proven unresponsive to conventional topical or systemic therapies.[3] Its development as a metabolite of etretinate reflects a common strategy in pharmaceutical development, where active metabolites are investigated for potentially improved pharmacokinetic or pharmacodynamic characteristics. The initial promise of a shorter duration of teratogenic risk due to acitretin's faster elimination compared to etretinate (half-life of approximately 49-63 hours for acitretin and its cis-isomer, versus approximately 120 days for etretinate [2]) was a significant driver for its adoption. However, the metabolic conversion to etretinate with alcohol consumption underscores the complexities that can arise in clinical pharmacology.

1.2. Identification