Variability of Skin Pharmacokinetic Data: Insights from a Topical Bioequivalence Study Using Dermal Open Flow Microperfusion.
Variability of Skin Pharmacokinetic Data: Insights from a Topical Bioequivalence Study Using Dermal Open Flow Microperfusion.
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DOI：
10.1007/s11095-020-02920-x
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发表时间：
2020-09-28
影响因子：
3.7
通讯作者：
Sinner F
中科院分区：
文献类型：
--
作者：
Bodenlenz M;Augustin T;Birngruber T;Tiffner KI;Boulgaropoulos B;Schwingenschuh S;Raney SG;Rantou E;Sinner F
皮肤开放流微灌注（dOFM）先前已证明其在临床研究中用于评估局部药物产品的生物等效性（BE）。我们的目的是表征该研究中皮肤药代动力学数据的变异性来源。利用来自20名健康成人的临床dOFM研究的多变量数据进行探索性统计分析，该研究评价了奥地利试验（T）和美国参考（R）阿昔洛韦乳膏（5%产品）的BE或缺乏BE。logAUC值的总体变异性（CV：R为39%，T为45%）主要由受试者间变异性（R：82%，T：91%）决定，受试者间变异性与受试者的皮肤电导最相关。受试者内变异性占总体变异性的18%（R）和9%（T）;皮肤治疗部位或方法学因素对该变异性无显著影响。受试者间变异性是阿昔洛韦总体变异性的主要组成部分，治疗部位位置对受试者内变异性没有显著影响。这些结果支持在同一受试者中同时评估T和R产品的dOFM BE研究设计，其中T和R治疗部位不一定需要彼此相邻。皮肤微观结构的局部变化可能是受试者内变异的主要原因。
Dermal open flow microperfusion (dOFM) has previously demonstrated its utility to assess the bioequivalence (BE) of topical drug products in a clinical study. We aimed to characterize the sources of variability in the dermal pharmacokinetic data from that study. Exploratory statistical analyses were performed with multivariate data from a clinical dOFM-study in 20 healthy adults evaluating the BE, or lack thereof, of Austrian test (T) and U.S. reference (R) acyclovir cream, 5% products. The overall variability of logAUC values (CV: 39% for R and 45% for T) was dominated by inter-subject variability (R: 82%, T: 91%) which correlated best with the subject’s skin conductance. Intra-subject variability was 18% (R) and 9% (T) of the overall variability; skin treatment sites or methodological factors did not significantly contribute to that variability. Inter-subject variability was the major component of overall variability for acyclovir, and treatment site location did not significantly influence intra-subject variability. These results support a dOFM BE study design with T and R products assessed simultaneously on the same subject, where T and R treatment sites do not necessarily need to be next to each other. Localized variation in skin microstructure may be primarily responsible for intra-subject variability.
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影响因子：
6.5
作者：
Benfeldt, Eva;Hansen, Steen H.;Shah, Vinod P.
通讯作者：
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影响因子：
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作者：
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DOI：
10.1016/j.ejpb.2009.12.003
发表时间：
2010-03-01
影响因子：
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作者：
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通讯作者：
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影响因子：
4.5
作者：
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