[Pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adult and paediatric patients with atopic dermatitis].
BACKGROUND
Safety concerns related to systemic immunosuppressive therapy have raised questions regarding systemic exposure to topically applied tacrolimus.


OBJECTIVE
To summarise all currently available information on the pharmacokinetics of tacrolimus ointment and to compare it with the pharmacokinetics of systemic use of tacrolimus.


RESULTS
Low and highly variable systemic exposure has been shown in pharmacokinetic studies of tacrolimus ointment performed in patients (adults and children) with moderate to severe atopic dermatitis. Patients with larger treatment areas tended to have higher exposure to the drug, but there was no evidence of systemic accumulation. Overall, 96, 92 and 97% of the blood samples assayed contained tacrolimus concentrations below 1 ng/ml, and 23, 17 and 20% of samples were below 0.025 ng/ml (the lower limit of quantification) in adults, children aged 6-12 and infants aged 3-24 months, respectively.


CONCLUSIONS
Although tacrolimus applied topically is absorbed systemically, the overall exposure as measured by the area under the curve (AUC)0-24 is low and highly variable. The extent of systemic exposure is higher in patients with larger treatment areas, but even in patients with up to 75% of the body surface area treated, the systemic exposure is substantially lower than that measured in transplant patients. Systemic exposure to tacrolimus tends to decrease as the skin lesions heal and there is no evidence of systemic accumulation despite repeated applications of ointment. The tacrolimus ointment was efficacious and well-tolerated.
Undre
N A
NA
Farmacocinética, Astellas Pharma GmbH, Munich, Alemania. Nas.Undre@eu.astellas.com
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000097:blood / Q000188:drug therapy*; D006084:Graft Rejection / Q000097:blood / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007223:Infant; D007408:Intestinal Absorption; D009824:Ointments; D012869:Skin Absorption; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D009824:Ointments; D016559:Tacrolimus