Pharmacokinetics of 0.1% Tacrolimus Ointment After First and Repeated Application to Adults with Moderate to Severe Atopic Dermatitis

The systemic exposure to tacrolimus after first and repeated application of 0.1% tacrolimus ointment was investigated in 32 adults with moderate to severe atopic dermatitis. Patients were allocated to treatment groups according to the size of the affected area to be treated: Group 1≤3000 cm2 (N=11); Group 2>3000 cm2≤6000 cm2 (N=12); Group 3>6000 cm2≤10,000 cm2 (N=9). Ointment was applied twice daily for 13 d and once daily on Day 14; the size of application area remained the same irrespective of healing. Blood samples were collected on Days 1 (first application), 4, and 14 (last application) and analyzed by a validated HPLC-MS/MS method. Systemic exposure to tacrolimus was generally low with 96% of blood samples assayed containing concentrations below 1 ng per mL and 23% of samples below the lower limit of quantification (0.025 ng per mL). Peak concentrations after first ointment application were ≤2.8 ng per mL, and the mean area under the concentration-time curve between 0 and 12 h using the trapezoidal rule (AUC0-12) values were 1.1, 1.6, and 4.8 ng h per mL for Groups 1, 2, and 3, respectively. The corresponding mean values on Day 14 were similar indicating negligible systemic accumulation of tacrolimus after repeated ointment applications. Both the rate and extent of topical absorption decreased as the skin lesions healed.