1. ^*Great Ormond Street Hospital for Children, London, UK
2. ^†Skin Therapy Research Unit, University Hospital Lewisham and Kings College London, London, UK
3. ^‡Medical Academy of Latvia, Riga, Latvia
4. ^§South Infirmary Victoria Hospital, Cork, Ireland
5. ^¶Hospital de la Santa Creu i Sant Peu, Barcelona, Spain
6. ^#Fujisawa GmbH, Munich, Germany

Correspondence: Nasrullah Undre, Fujisawa GmbH, Neumarkter Strasse 61, 81673 Munich, Germany. Email: nas.undre@fujisawa.de

Received 29 July 2004; Revised 20 September 2004; Accepted 27 October 2004.

Abstract

The pharmacokinetics of tacrolimus after first and repeated application of 0.1% tacrolimus ointment were evaluated in 39 children, aged 6–12 y, with moderate to severe atopic dermatitis. The patients were grouped according to the size of the affected body surface area to be treated: Group 11500 cm²; Group 2 >1500 cm²3000 cm²; Group 3 >3000 cm²5000 cm². Serial blood samples to calculate pharmacokinetic parameters taken on Day 1 (first ointment application) and Day 14 (last application) showed minimal systemic exposure to tacrolimus. Overall, 92% of the blood samples assayed contained tacrolimus concentrations below 1 ng per mL and 17% of samples were below 0.025 ng per mL, the lower limit of quantification. Systemic exposure to tacrolimus varied between patients and tended to increase proportionally as the size of the treated body surface area increased. Absorption decreased with time as the skin lesions healed and there was no evidence of systemic accumulation. The mean apparent half-life of tacrolimus (t_{1/2, z}) was 6627 h (range 19–125 h). Most patients experienced substantial clinical improvement in their atopic dermatitis. There were no clinically relevant changes in laboratory values, and the most frequently reported adverse event was skin burning, which resolved quickly as the skin condition improved.