Suction blister fluid.
Etretinate (Ro 10-9359) is beneficial in psoriasis and various keratinization disorders [5,6]. The drug has an ethyl ester group as a polar end group, and after oral administration it is hydrolyzed to the corresponding acid Ro 10-1670 [2]. So far it is not known to what extent these two compounds are responsible for the biologic effects of the drug in the target tissue. Both compounds reach their peak plasma concentration within 3 -6 h [9]. The terminal elimination half-life of Ro 10-9359 is between 2 and 3 months, which can only be detected after cessation of a long-term treatment [7,9]. This suggests that storing takes place at some yet unknown storage site [7]. In the present study we determined the levels of Ro 10-9359 and its main metabolite Ro 10-1670 in plasma and suction blister fluid after 2 and 6 weeks of treatment.
Five patients with psoriasis were studied [two women, three men; age: 50 +_ 8 years (mean + SEM), weight 77 _+ 4 kg]. Ro 10-9359 was administered in capsules of either 25 or 10 mg two or three times daily. The dose of all patients during the initial 2 weeks of treatment was 60 rag/day (0.7-0.9 mg/kg). The dose was later reduced according to the individual clinical response, being 40 β’ 9 mg (0.4-0.8 mg/kg) at the end of the 6th week. The cumulative drug dose was 944 + 46 mg after 2 weeks and 2,203 + 105 mg after 6 weeks of treatment. The concentrations of Ro 10-9359 and Ro 10-1670 in plasma and suction blister fluid were determined after 2 and 6 weeks of treatment. Eight hours after the last dose suction blisters were formed on uninvolved skin by the method described previously [4]. This was accomplished in 1.5-2 h, after which the blood samples (10 ml) and the blister fluid samples (1 -2 ml) were taken into light-protected glass tubes in a darkened room. The concentrations of Ro 10-9359 and Ro 10-1670 in plasma and blister fluid were determined by high performance liquid chromatography as described previously [3].
The level of Ro 10-9359 in the plasma of the five psoriatics ranged from 95 to 317 ng/ml after 2 weeks and from 47 to 390 ng/ml after 6 weeks of treatment. The ranges of Ro 10-1670 in plasma were 60-119 ng/ml and 9-132 ng/ml.