The pharmacokinetics of tacrolimus after first and repeated dosing with 0.03% ointment in infants with atopic dermatitis*

Authors

  • Sakari Reitamo MD,

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • Johanna Mandelin MD,

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • Andris Rubins MD,

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • Anita Remitz MD,

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • Mika Mäkelä MD,

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • Kristine Cirule MD,

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • Silvestrs Rubins MD,

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • Sanita Zigure MD,

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • Vincent Ho,

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • James Dickinson MSc,

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • Nasrullah Undre PhD

    1. From the Department of Dermatology, Helsinki University Hospital, Helsinki, Finland, Latvijas Dermatologijas Instituta Klinika, Riga, Latvia, and Clinical Trials, Skin Care Center, Vancouver, Canada; Department of Pharmacokinetics, Astellas Pharma GmbH, Munich, Germany
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  • *

    Tacrolimus ointment is not licensed for use in children below 2 years of age.

Nasrullah Undre Astellas Pharma GmbH Neumarkter Str. 61 81673 Munich Germany E-mail: nas.undre@eu.astellas.com

Abstract

Background  In adults and children aged > 2 years, systemic absorption of tacrolimus from tacrolimus ointment is very low. In this study, the pharmacokinetics of tacrolimus 0.03% ointment were investigated in infants aged 3–24 months.

Methods  The pharmacokinetics of tacrolimus after first and repeated topical application of tacrolimus 0.03% ointment were evaluated in 53 infants (age, 3–24 month) with atopic dermatitis requiring treatment with mid-potency topical corticosteroids. Patients were grouped according to percentage of body surface area affected (Group 1: 5–20%; Group 2: > 20–40%; Group 3: > 40%). After stratification, patients were randomized (double-blind) to receive once-daily or twice-daily tacrolimus 0.03% ointment.

Results  Blood samples taken on days 1 and 14 (first and last application) showed minimal systemic tacrolimus exposure. Overall, 97% of blood samples assayed contained tacrolimus concentrations < 1 ng/ml, and 20% were below the lower limit of quantification (0.025 ng/ml). Systemic tacrolimus exposure was variable, but tended to increase as the treated body surface area increased. Mean apparent half-life of tacrolimus was 80 ± 35 h (range: 25–175 h). Most patients experienced substantial clinical improvement in their atopic dermatitis. There were no clinically significant changes in laboratory values, and the most frequently reported adverse events were minor infections and local skin irritations.

Conclusions  Tacrolimus 0.03% ointment in infants is associated with very low systemic exposure to tacrolimus. Treatment was well tolerated and led to considerable clinical improvement.

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