Low systemic exposure in infants with atopic dermatitis in a 1‐year pharmacokinetic study with pimecrolimus cream 1%*

Lakhanpaul, Monica; Davies, Timothy; Allen, B.R.; Schneider, D.

doi:10.1111/j.1600-0625.2006.00398.x

Cited by 46 publications

(46 citation statements)

References 9 publications

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“…[99]. Only minimal systemic resorption of pimecrolimus was observed after treatment with the 1% cream and no systemic effects considered to be treatment related [100,101,102,103,104]. …”

Section: Pimecrolimusmentioning

confidence: 99%

Discovery of Topical Calcineurin Inhibitors and Pharmacological Profile of Pimecrolimus

Stuetz

Baumann

Grassberger

et al. 2006

Int Arch Allergy Immunol

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Using a newly developed model of allergic contact dermatitis in pigs, calcineurin inhibitors of the tacrolimus and ascomycin type were shown to have a highly anti-inflammatory action after topical application. These findings provided the first pharmacological evidence of the efficacy of this novel class of topical agents in the treatment of inflammatory skin diseases, and, thus, their potential to become the first alternative to corticosteroids in more than 40 years. As a result of a large research program into ascomycins, pimecrolimus (Elidel®, SDZ ASM 981) was selected for development due to its favorable pharmacology and safety profile, alongside tacrolimus (Protopic®, FK 506). In vitro, pimecrolimus inhibits the transcription and release of pro-inflammatory cytokines in T cells. Similar to the corticosteroids, betamethasone-17-valerate and dexamethasone, pimecrolimus is effective at nanomolar concentrations. Targeting mainly T cells, pimecrolimus has, however, a more specific mode of action. Moreover, in contrast to corticosteroids, pimecrolimus has no effect on Langerhans’ cells, the professional antigen- presenting dendritic cells of the skin that are crucial for local immunosurveillance. When applied topically, pimecrolimus exerts a high and selective anti-inflammatory activity in the skin, shows minimal percutaneous absorption, and has a low potential to affect systemic immunoreactions. Pimecrolimus cream 1% has proven to be well tolerated, safe, and highly effective in clinical studies in patients with atopic dermatitis.

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“…[99]. Only minimal systemic resorption of pimecrolimus was observed after treatment with the 1% cream and no systemic effects considered to be treatment related [100,101,102,103,104]. …”

Section: Pimecrolimusmentioning

confidence: 99%

Discovery of Topical Calcineurin Inhibitors and Pharmacological Profile of Pimecrolimus

Stuetz

Baumann

Grassberger

et al. 2006

Int Arch Allergy Immunol

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“…In the studies discussed above, pimecrolimus blood concentrations remained low during the treatment periods for up to 1 year [22, 23, 30, 32, 33], indicating that there was no systemic accumulation of the drug over time. Pimecrolimus blood levels were in a comparable range in infants and children [32].…”

Section: Pharmacokinetic Profilementioning

confidence: 99%

“…Five infants completed one year in the study [33]. Pimecrolimus blood concentrations were <2 ng/ml in 93% of samples and below the LoQ (0.5 ng/ml) in 60% of samples [33]. The maximum blood concentration measured during the 1-year period was 1.9 ng/ml [33].…”

Section: Pharmacokinetic Profilementioning

confidence: 99%

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An Update on the Safety and Tolerability of Pimecrolimus Cream 1%: Evidence from Clinical Trials and Post-Marketing Surveillance

et al. 2007

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In this report, we review the data on the safety and tolerability of pimecrolimus cream 1% (Elidel®) from clinical trials and post-marketing surveillance in patients with atopic dermatitis. These data demonstrate that topically applied pimecrolimus is minimally absorbed through the skin and has afavourable safety margin. The most common treatment-related adverse events are transient local reactions, particularly skin burning (16.1 and 12.9 events per 1,000 patient-months of follow-up in adults and children, respectively). When compared to the vehicle, the use of pimecrolimus cream 1% is associated with an increased incidence of herpes simplex virus infections in children (relative risk: 2.5; 95% confidence interval: 1.2–5.8; p = 0.017). However, pimecrolimus cream 1% does not increase the incidence of any skin infection in comparison with moderately potent topical corticosteroids and lacks other corticosteroid-related side effects such as skin atrophy. While cases of malignancy have been reported in patients who have used pimecrolimus cream 1%, there is no clinical evidence to establish that treatment with pimecrolimus cream 1% increases the risk of malignancy.

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“…In addition, pimecrolimus cream reduces the requirement of topical corticosteroids in the management of severe pediatric AD [6]. Pimecrolimus has a favorable tolerability and safety profile in adults, adolescents and children and is absorbed at very low levels even in children [7,8]. …”

Section: Introductionmentioning

confidence: 99%

Percutaneous Absorption of Pimecrolimus Is Not Increased in Patients with Moderate to Severe Atopic Dermatitis when Pimecrolimus Cream 1% Is Applied under Occlusion

Thaçi

Kaufmann²,

Bieber³

et al. 2010

Dermatology

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Aim: To evaluate the systemic exposure of pimecrolimus cream 1% applied under occlusion in atopic dermatitis (AD) patients. Methods: A noncomparative, open-label study conducted in 3 groups of moderate to severe AD patients: A (adults, n = 9), B (adolescents, n = 4) and C (children, n = 6). Pimecrolimus cream 1% was applied twice daily for 8.5 days with overnight occlusion in patients with investigator’s global assessment scores of ≧3 and AD involving at least 30% of their body surface area. Pimecrolimus blood concentrations were analyzed. Results: The highest pimecrolimus blood concentrations observed in adults, adolescents and children were 1.84, 0.55 and 1.29 ng/ml, respectively. Pimecrolimus blood concentrations and affected body surface area showed no apparent correlation. Conclusion: No measurable differences were found in pimecrolimus blood concentrations, efficacy and safety profile when pimecrolimus cream 1% was applied under occlusion versus application without occlusion. These findings reflect the high lipophilic properties of pimecrolimus.

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Low systemic exposure in infants with atopic dermatitis in a 1‐year pharmacokinetic study with pimecrolimus cream 1%*

Cited by 46 publications

References 9 publications

Discovery of Topical Calcineurin Inhibitors and Pharmacological Profile of Pimecrolimus

Discovery of Topical Calcineurin Inhibitors and Pharmacological Profile of Pimecrolimus

An Update on the Safety and Tolerability of Pimecrolimus Cream 1%: Evidence from Clinical Trials and Post-Marketing Surveillance

Percutaneous Absorption of Pimecrolimus Is Not Increased in Patients with Moderate to Severe Atopic Dermatitis when Pimecrolimus Cream 1% Is Applied under Occlusion

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