Etretinate, isotretinoin (13-cis-retinoic acid), and tretinoin (all-trans-retinoic acid) are retinoic acid analogues comprising a group of compounds known as the retinoids. However, they exhibit distinct and important differences with regard to their therapeutic and toxicological profiles. Tretinoin, due to a low oral therapeutic index, is limited almost exclusively to topical application, whereas etretinate and isotretinoin are therapeutically effective when given systemically by the oral route.Clinical doses of isotretinoin range from 0.5 to 8 mg/kg/day, with acute side effects appearing following doses of 1 mg/kg/day or greater. Plasma concentrations of isotretinoin following single and multiple doses peak between 2 to 4 hours and exhibit elimination half-lives of 10 to 20 hours. Isotretinoin blood concentration-time curves following a singleor multiple-dose regimen are well described by a linear model with biphasic disposition characteristics.Etretinate, which possesses a narrower therapeutic concentration range than isotretinoin, is used clinically at doses between 0.5 to 1.5 mg/kg/day; acute side effects appear following doses of 0.5 mg/kg/day or more.In most conditions, the retinoids produce a maximal effect in about 8 weeks (at the highest tolerated dose), with a slow recurrence of symptoms usually occurring within several weeks following cessation of treatment - except in the treatment of cystic acne with isotretinoin. Maintenance or intermittent dosing usually results in a prolongation of remission.Pharmacokinetically, the major difference between isotretinoin and etretinate is the much longer elimination half-life (120 days) of etretinate following long term administration. Recently, however, blood concentrationversustime curves from day 1 to day 180 of etretinate therapy have been fitted by a single polyexponential pharmacokinetic equation without the need to invoke non-linearity in the kinetics. The observed lengthening of the elimination half-life with multiple dosing may thus be due to a lack of assay sensitivity at drug concentrations seen after single-dose administration, rather than to time-related alterations in the pharmacokinetics of etretinate.