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Pharmacokinetics of topical calcineurin inhibitors in adult atopic dermatitis: A randomized, investigator-blind comparison

https://doi.org/10.1016/j.jaad.2005.06.013Get rights and content

Objective

We sought to compare pharmacokinetics of pimecrolimus cream 1% and tacrolimus ointment 0.1% in adults with extensive, moderate to severe atopic dermatitis. Secondary end points included efficacy and safety.

Methods

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).

Results

Tacrolimus was detectable in 36% of blood samples and pimecrolimus was detectable in 12%. In patients with measurable blood drug concentrations, systemic exposure to tacrolimus (mean area under the curve0-10h < 9.7 ng·h/mL; n = 7) was higher than to pimecrolimus (mean area under the curve0-10h < 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 for the majority of patients with atopic dermatitis who have mild to moderate disease.

Conclusion

Pimecrolimus appears to be associated with lower systemic drug exposure than tacrolimus.

Section snippets

Study design

This was a randomized, investigator-blind, parallel-group, multicenter trial. Adult patients with moderate to severe AD (Investigators' Global Assessment8 [IGA] score of 3-5) affecting at least 30% of the total body surface area (TBSA) received twice-daily treatment with either pimecrolimus or tacrolimus for 13 days. An investigator-blind design was used because the formulation differences between the two study treatments made it impossible to conduct the study in a double-blind manner.

Patients

Patients

Patients

A total of 37 patients was randomized at 6 centers in the United States to receive either pimecrolimus (n = 18) or tacrolimus (n = 19). Baseline demographics are shown in Table I. In general, the two treatment groups had similar baseline demographic characteristics, with some slight imbalances in the proportion of women (12 of 18 in the pimecrolimus group and 17 of 19 in the tacrolimus group) and mean body weight (83 kg in the pimecrolimus group and 71.9 kg in the tacrolimus group). The mean

Discussion

Previously published studies have demonstrated that systemic absorption through the skin in most patients with AD who were treated with topical calcineurin inhibitors is negligible. Concentrations of the active compound in the blood were low or undetectable, even in the most susceptible patients, such as those with extensive disease and high body area to mass ratios, and pediatric patients.2, 3, 4, 5, 6, 7 However, significant absorption of topical tacrolimus has been reported in patients with

References (23)

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    Validation of the Eczema Area and Severity Index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials program

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  • Cited by (55)

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      Systemic absorption of topical tacrolimus is low, and available data suggest the risk of congenital defects is not increased.2,17 Although topical pimecrolimus is absorbed even less,18 its FDA label currently says not to use because of lack of experience. Topical tacrolimus is recommended because of a large amount of existing data and may be preferable to TCS especially for use on the face and areas prone to striae formation.2

    • Atopic dermatitis and pregnancy

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      Although an increased risk of prematurity has been demonstrated, it may be associated with maternal disease.55 Furthermore, because of the large size of the molecules, systemic absorption of tacrolimus and pimecrolimus is considered to be very low.56,57 Although not approved for use during pregnancy, topical calcineurin inhibitors can be recommended for the face, intertriginous areas, and thigh skin, where the use of TCSs is not favorable due to the risk of striae formation (Fig 5).49

    • Topical Calcineurin Inhibitors

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    Funding source: Novartis Pharmaceuticals Corp.

    Disclosure: Ms Chon and Dr Abrams are employees of Novartis Pharmaceuticals Corp. Dr Paul is an employee of Novartis Pharma AG.

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