Determination of Acitretin and 13<i>-cis-</i>Acitretin in Skin

Abstract

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.

The distribution of cis‐ and trans‐acitretin in human epidermis.

“…Estimates of AUC values of both isomers are given in Table 1. Our findings do not support the suggestion of Laugier et al (1989) that acitretin may accumulate in the epidermis, since its concentration in the first blister roof before drug intake on day 13 (i.e. 24 h after the previous drug intake) was below the limit of assay.…”

Teratogenic Risk with Etretinate and Acitretin Treatment

“…This is explained by the high lipophilicity of etretinate and its storage in fatty tissues from which small amounts of the drug are slowly released [2lJ. After treatment cessation, acitretin is measurable in the skin in cluding subcutaneous fat whereas it has already reached un detectable levels in plasma [22], Taking into account the slow elimination of etretinate, the recommended postther apy contraception time is 2 years. A 2-month period was initially proposed for acitretin.…”

Determination of Acitretin in the Skin, in the Suction Blister, and in Plasma of Human Volunteers after Multiple Oral Dosing

“…Plasma pharmacokinetics of etretinate, acitretin, and its metabolites, as well as concentrations of etretinate during long-term therapy in skin and other organs have been investigated e x t e n~i v e l y .~.~~~ In contrast, acitretin concentration determinations and acitretin metabolism in the skin after multiple dosing as well as after cessation of the treatment are infrequently reported. [9][10][11] Appropriate dosage regimens are often based on the relations of time, concentration at the active site (biophase), and drug response in humans. For reasons of feasibility, correlation of drug effects and drug concentration in blood are most often looked for and satisfactory correlations are often found.…”