Bioequivalence of topical formulations in humans:: Evaluation by dermal microdialysis sampling and the dermatopharmacokinetic method
Bioequivalence of topical formulations in humans:: Evaluation by dermal microdialysis sampling and the dermatopharmacokinetic method
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DOI：
10.1038/sj.jid.5700495
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发表时间：
2007-01-01
影响因子：
6.5
通讯作者：
Shah, Vinod P.
中科院分区：
文献类型：
--
作者：
Benfeldt, Eva;Hansen, Steen H.;Shah, Vinod P.
本研究的目的是评价皮肤微透析（DMD）采样和皮肤药代动力学方法同时用于局部制剂的生物等效性（BE）研究之间的关系。在8名健康志愿者（4名男性，4名女性）中研究了局部利多卡因乳膏和软膏（均为5%）。在一只前臂上，在两个渗透区域中的四个微透析探针取样5小时，并且在另一只手臂上，在产品应用后30和120分钟进行胶带剥离。采用高效液相色谱-质谱联用法分析样品中利多卡因的含量。这两种方法一致，表明乳膏制剂的利多卡因渗透率比软膏制剂高3- 5倍。在120分钟时，证明了微透析液与胶带剥离中利多卡因含量的两种方法之间的等级顺序相关性，对于软膏制剂和一起分析的两种制剂具有显著性。方差分析表明，微透析液中的利多卡因浓度可重现，探针之间的受试者内变异性为19%，两个渗透区域之间的变异性为20%。因此，受试者间变异性占方差的61%。DMD采样证明是有效的，变异性分析证明了在18例受试者中进行BE研究的可行性。
The aim of this study was to evaluate the relationship between dermal microdialysis (DMD) sampling and the dermatopharmacokinetic method when employed simultaneously for bioequivalence (BE) investigations of topical formulations. Topical lidocaine cream and ointment (both 5%) was investigated in eight healthy human volunteers (four male, four female). On one forearm, four microdialysis probes in two penetration areas sampled for 5 hours, and on the other arm, tape stripping was performed 30 and 120 minutes after product application. Lidocaine content in samples was analyzed by HPLC-mass spectrometry. The two methods were in agreement showing 3- to 5-fold higher liclocaine penetration from cream formulation than from ointment. A rank-order correlation between the two methods was demonstrated for lidocaine contents in microdialysates versus tape strip at 120 minutes, significant for the ointment formulation and for both formulations analyzed together. Analysis of variance demonstrated reproducible lidocaine concentrations in microdialysates with an intrasubject variability of 19% between probes and 20% between the two penetration areas. Thus, intersubject variability accounted for 61% of the variance. DMD sampling proved effective and variability analyses demonstrated the feasibility of BE studies in as little as 18 subjects.