Pharmacokinetics of Tacrolimus Following Topical Application of Tacrolimus Ointment in Adult and Pediatric Patients with Moderate to Severe Atopic Dermatitis

Objective: To characterize the pharmacokinetics of tacrolimus after topical application in adult and pediatric patients with moderate to severe atopic dermatitis from all clinical trials in which tacrolimus blood levels were obtained.

Methods: Tacrolimus ointment 0.03% or 0.1% was applied twice daily. In the adult and pediatric pharmacokinetic studies, serial blood samples were obtained after single and repeated topical application. During the 12 clinical efficacy trials of tacrolimus ointment, single blood samples were obtained at various times relative to tacrolimus ointment application.

Results: In the pharmacokinetic studies, 89% to 95% of tacrolimus whole blood concentration samples were less than 1 ng/mL; mean maximum concentrations ranged from 0.2 to 1.6 ng/mL and mean area under the blood concentrationtime curves (0-12 hours) ranged from 1.4 to 13.1 ng·hr/mL. Likewise, in the clinical efficacy trials, the majority (85%- 99%) of tacrolimus concentration samples were less than 1 ng/mL.

Conclusions: Tacrolimus ointment is associated with minimal systemic absorption and no evidence of systemic accumulation in patients with moderate to severe atopic dermatitis and extensive disease.