The pharmacokinetics of pimecrolimus cream 1% and tacrolimus ointment 0.1% in adults with extensive, moderate to severe atopic dermatitis, including systemic absorption, has relevance to patient safety and drug efficacy. Past pharmacokinetic studies have demonstrated that most patients with atopic dermatitis treated with topical calcineurin inhibitors experience negligible systemic absorption, resulting in low or undetectable blood concentrations of the active compound, but have not compared these two agents directly.
Calcineurin inhibitors, also called immunomodulatory are common agent to regulate the immune system and blocks inflammation associated with eczema. Calcineurin inhibitors are often used as an alternative to topical corticosteroids or when other treatments have failed or lead to unwanted side effects. In contrast to topical corticosteroids and topical calcineurin inhibitors do not thin the skin and may in sensitive areas such as the face and eyelids, where corticosteroids are avoided be applied. Calcineurin inhibitors are usually for short-term treatment of 2 years and older prescribed with a healthy immune system. Short-term treatment may be repeated.
Pimecrolimus appears to be associated with lower systemic drug exposure than tacrolimus. This study was a randomized, investigator-blind, parallel-group, multicentre trial. Adult patients with moderate to severe atopic dermatitis (Investigators’ Global Assessment score of 3–5) affecting at least 30% of the total body surface area received twice-daily treatment with either pimecrolimus and tacrolimus for 13 days. Patients received twice-daily treatment for 13 days. Blood concentrations of pimecrolimus and tacrolimus were measured at days 1, 5 and 13. Treatment success was defined as an Investigators’ Global Assessment score of 0 (clear) or 1 (almost clear). Thirty-seven patients were randomized at six centres in the USA to receive either pimecrolimus (n = 18) or tacrolimus (n = 19). A greater proportion of patients treated with tacrolimus had detectable levels of drug in their blood compared with those treated with pimecrolimus (36 vs 12%). Blood concentrations of tacrolimus were higher than those of pimecrolimus in both men and women. Tacrolimus is currently indicated for patients with moderate to severe Atopic Dermatitis, whereas pimecrolimus is indicated for patients with mild to moderate disease.
In patients with measurable blood drug concentrations, systemic exposure to tacrolimus (mean area under the curve 0–10h <9.7 ng/h/ml; n = 7) was higher than to pimecrolimus (mean area under the curve 0–10h <2.5 ng/h/ml; n = 2). Whole-body treatment success (day 13) was achieved in 1 of 18 (5.6%) and 2 of 19 (10.5%) patients treated with pimecrolimus and tacrolimus respectively, and face/neck treatment success in 5 of 18 (27.8%) and 5 of 19 (26.3%) patients respectively. Patients included in the study were adult patients with severe atopic dermatitis. The results and conclusions drawn from this study population may not be applicable to the majority of patients with atopic dermatitis, who have mild to moderate disease.
Pimecrolimus is highly lipophilic, and systemic absorption is negligible even in patients with extensive areas treated. As a non-steroidal drug, pimecrolimus does not induce skin atrophy and can be used for extended periods to control early manifestations of atopic dermatitis. This study was conducted over a relatively short period and longer-term studies of patients with severe disease are warranted.
