Pharmacokinetics and therapeutic efficacy of retinoids in skin diseases

Abstract

The retinoids are a class of compounds that includes the natural forms and synthetic analogues of vitamin A. Isotretinoin, often referred to as a first generation retinoid, may be of considerable benefit to patients with severe, recalcitrant acne. Etretinate and acitretin, 2 aromatic compounds representing the second generation, have found their major success in the treatment of psoriasis, particularly in combination with more traditional therapies. Retinoid therapy is associated with a distinctive adverse effect profile typical of hypervitaminosis A; thus, it is especially important that fertile women undergoing retinoid therapy adhere to a contraceptive regimen. These drugs are extensively metabolised and only traces of unchanged drugs are eliminated in urine. The terminal elimination half-lives of isotretinoin, etretinate and acitretin after long term treatment are up to 20h, 120 days and 48h, respectively. Because of lack of definite correlation between plasma concentration and desired pharmacological effects, in conjunction with the very pronounced inter- and intraindividual variation in systemic availability (15 to 90%) after oral administration of these drugs, initial dosages in individual patients can only be roughly judged on the basis of the general pharmacokinetics of the agents. Later dosage adjustments should be made on the basis of monitoring of both plasma drug (and possible metabolite) concentrations, and the efficacy and tolerability of the drugs.