Jean-Marie Geiger

Photochemotherapy for severe psoriasis without or in combination with acitretin: A randomized, double-blind comparison study

In a randomized, double-blind comparative study 60 patients with severe, widespread psoriasis were treated either with photochemotherapy (PUVA) alone or in combination with acitretin. Forty-eight patients completed the study; of these, 25 received placebo combined with PUVA and 23 received acitretin with PUVA. Marked or complete clearing of psoriasis occurred in 80% of the patients (20 of 25) without acitretin and in 96% of the patients (22 of 23) with adjunctive acitretin administration. The mean cumulative UVA dose given to patients in the acitretin-PUVA group was 42% less than that required for patients in the placebo-PUVA group. We conclude that acitretin substantially augments the efficacy of photochemotherapy in the treatment of severe psoriasis.

Acitretin in the treatment of severe disorders of keratinization: Results of an open study

The purpose of this open, noncomparative study with acitretin (Ro 10-1670) was to evaluate the clinical response of patients with various nonpsoriatic disorders of keratinization and to establish for these patients the optimal dosage for both efficacy and tolerance. Thirty-three patients (21 adults and 12 children or adolescents) with ichthyoses, palmoplantar hyperkeratosis, or Dariers disease were treated for a period of 4 months. Most patients showed marked improvement or remission. The results obtained in congenital ichthyosiform erythroderma, lamellar ichthyosis, and Papillon-Lefèvre syndrome were judged as better than those usually reported with etretinate. The side effects observed in our patients were similar to those reported with etretinate, with the exception of scaling of palms and soles, which had an incidence and severity greater than expected with etretinate. The optimal acitretin dosage providing the best efficacy with minimal undesirable effects varied from patient to patient. The mean daily dose (+/- SD) was 27 +/- 11 mg in adults and 0.7 +/- 0.2 mg/kg in children or adolescents.

Vaginal Keratinization during the Estrous Cycle in Rats: A Model for Evaluating Retinoid Activity

A model is described for evaluating the activity of a retinoid based on its effect on the keratinization of the vaginal epithelium that occurs on estrus (day 4) of a 4-day cycle in female rats. This keratinization process is dependent on the endogenous estradiol (E2) secreted between the evening of diestrus 2 (day 2) and that of proestrus (day 3). Various doses of all-transretinoic acid (tRA) were injected at different time points during the estrous cycle and the vaginal keratinization was assessed by microscope examination of unstained native or Papanicolaou-stained smear preparations. Additionally, the preovulatory E2 secretion was measured and ovaries were histologically examined. A single injection of 10 mg/kg tRA either on diestrus 2 (evening) or on proestrus (early morning) was able to induce a complete inhibition of the vaginal keratinization in more than 80% of the cases. This can be considered as a direct effect on the vaginal epithelial differentiation since neither the E2 secretion nor the ovulatory process were affected. The inhibition of vaginal keratinization can be used as a rapid and convenient in vivo model for screening retinoid candidates with antikeratinizing activity.

Determination of Acitretin and 13-cis-Acitretin in Skin

The aim of the study was to investigate the concentrations of Ro 10-1670 (acitretin) and its isomeric metabolite Ro 13-7652 (cis-acitretin) after multiple oral dosing of acitretin. We used a highly sensitive HPLC method for simultaneous determination of the 2 retinoids with a quantification limit of 2 ng/ml in plasma and 10 ng/g in total skin (epidermis and dermis). In hairless rats receiving orally 8 mg/kg acitretin once daily during 8 days, blood and skin samples were taken at different time points between 5 and 96 h after the last dose. After 96 h, appreciable concentrations of Ro 10-1670, but not Ro 13-7652 could be measured in the skin, whereas both isomers were below the quantification limit in plasma. In psoriatic patients treated with a once daily dose of 30 mg acitretin, blood samples and biopsies were taken after 1 month of treatment (i.e. under steady state conditions). 24 h after the last drug intake, skin concentrations of acitretin were approximately 10 times higher than those observed in plasma. Ro 10-1670 concentrations in the skin were approximately 3-5 times higher than for Ro 13-7652 and concentrations of both isomers were higher in lesional compared to uninvolved skin.

Cis-trans Intelconversion of Acitretin in Man

The major plasma metabolite of acitretin (trans-acitretin) is its 13-cis isomer, cis-acitretin. Interconversion of cis -acitretin to trans-acitretin was demonstrated in man following administration of a single oral dose of cis -acitretin. Plasma concentrations of Ro 13–7652 (cis-acitretin) and Ro 10–1670 (trans-acitretin) were much higher after cis -acitretin administration than after trans-acitretin administration. Surprisingly, these high concentrations were not associated with a clear therapeutic effect in dermatoses (e.g. psoriasis) which are usually responsive to oral retinoids. Interactions between the cis and trans isomers formed in vivo may explain the difference in therapeutic activity of each stereoisomer when administered orally.

Determination of a New Retinoid: 9-CIS Retinoic Acid in Plasma by HPLC.

Abstract A method is described for the quantitative analysis of 9-cis retinoic acid in plasma. Following a simple extraction, the compounds are determined by reversed-phase high-performance liquid chromatography (HPLC) and detection at 350 nm. This method was applied to plasma specimens collected from rabbit which received by gorging a single dose administration of this compound but it could be applied too to human plasma.