Single Dose Pharmacokinetics of Etretin and Etretinate in Psoriatic Patients

Abstract

Etretin, an aromatic retinoic acid derivative, has recently been introduced as a possible substitute for etretinate in the treatment of severe psoriasis and other dyskeratoses. A total of nine patients with psoriasis of either sex in the age range 23-76 years was investigated after single dose oral drug administration, six were given 40 mg of etretin and three 40 mg of etretinate. A newly developed reversed-phase HPLC method was applied for simultaneous determination of etretin and etretinate in plasma. In patients receiving etretinate, the lag-time i.e. the time elapsing until appearance of first-order drug absorption was 1.24 .+-. 0.27 for the parent drug and 0.69 hrs .+-. 0.16 (mean value .+-. S.D.) for its metabolite etretin. Absorption half-times were 0.86 .+-. 0.04 and 0.55 hrs .+-. 0.09, respectively. The patients receiving etretin showed a lag-time of 0.42 hrs .+-. 0.23 and an absorption half-time of 0.33 hrs .+-. 0.28. This suggests that a fraction of etretinate is rapidly hydrolysed to etretin during the absorption process. The mean half-times of the distributory phases of disposition for etretinate and etretin were about 1 and 1.3 hrs and the apparent terminal half-lives were 6.57 .+-. 2.09 and 5.52 hrs .+-. 1.76, respectively. Assuming 40% systemic availability for both drugs the mean apparent volumes of distributions were calculated to be 1.50 .+-. 0.46 and 1.31 l .cntdot. kg-1 .+-. 0.53 and mean plasma clearances were 177.8 .+-. 105.8 and 175.9 ml .cntdot. kg-1 .cntdot. hr-1 .+-. 81.4 for etretinate and etretin, respectively. The pharmacokinetic data thus seems to indicate that etretin is absorbed faster after oral ingestion than etretinate, which is partially hydrolysed to etretin, possibly in the gut wall. After distribution about 71% of etretinate and 45% of etretin seems to reside outside of the initial distribution volume in the body.