Undre N A, Moloney F J, Ahmadi S, Stevenson P, Murphy G M
Department of Pharmacokinetics, Astellas Pharma GmbH, 81673 Munich, Germany.
Br J Dermatol. 2009 Mar;160(3):665-9. doi: 10.1111/j.1365-2133.2008.08974.x. Epub 2008 Dec 12.
Systemic exposure to tacrolimus following topical application of tacrolimus ointment is minimal. There are, however, no data on the distribution of tacrolimus in the skin.
To assess the distribution of tacrolimus in the skin and the systemic pharmacokinetics of tacrolimus in adults with moderate to severe atopic dermatitis after first and repeated application of tacrolimus ointment.
We investigated skin distribution of topically applied tacrolimus and systemic pharmacokinetics of percutaneously absorbed tacrolimus in adults with atopic dermatitis after topical application of tacrolimus 0.1% ointment twice daily for 2 weeks. Tacrolimus concentrations were assessed in full-thickness skin biopsies and blood samples.
Of 14 patients, 11 completed treatment and were analysed. Mean +/- SD tacrolimus concentrations in the skin at 24 h after first and last ointment applications were 94 +/- 20 and 595 +/- 98 ng cm(-3), respectively. At 168 h after stopping treatment, values were 97% lower than at 24 h after last application. Tacrolimus concentration decreased with increasing skin depth. Systemic tacrolimus exposure after ointment application was low and highly variable, with 31% of samples below the limit of quantification (0.025 ng mL(-1)) and 94% below 1 ng mL(-1). Blood concentrations at 24 h after the first and last ointment applications were 750 and 1800 times lower, respectively, than those in skin. Physicians' assessments showed that tacrolimus ointment was effective and well tolerated.
Tacrolimus was primarily partitioned in the skin, with minimal systemic absorption after topical application, in patients with atopic dermatitis.
外用他克莫司软膏后全身吸收他克莫司的量极少。然而，目前尚无关于他克莫司在皮肤中分布的数据。
评估他克莫司软膏首次及重复应用后，中重度特应性皮炎成人患者皮肤中他克莫司的分布情况以及他克莫司的全身药代动力学。
我们研究了特应性皮炎成人患者外用0.1%他克莫司软膏每日两次、持续2周后，局部应用他克莫司在皮肤中的分布以及经皮吸收的他克莫司的全身药代动力学。对全层皮肤活检组织和血样中的他克莫司浓度进行了评估。
14例患者中，11例完成治疗并纳入分析。首次及末次软膏应用后24小时皮肤中他克莫司的平均浓度（均值±标准差）分别为94±20和595±98 ng/cm³。停药后168小时，该值比末次应用后24小时降低了97%。他克莫司浓度随皮肤深度增加而降低。软膏应用后全身他克莫司暴露量较低且差异很大，31%的样本低于定量限（0.025 ng/mL），94%低于1 ng/mL。首次及末次软膏应用后24小时的血药浓度分别比皮肤中的浓度低750倍和1800倍。医生评估显示他克莫司软膏有效且耐受性良好。
在特应性皮炎患者中，他克莫司主要分布于皮肤，外用后全身吸收极少。
