Single dose pharmacokinetics of etretin and etretinate in psoriatic patients

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 X kg-1 +/- 0.53 and mean plasma clearances were 177.8 +/- 105.8 and 175.9 ml X kg-1 X hr-1 +/- 81.4 for etretinate and etretin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)