Improved Bioequivalence Assessment of Topical Dermatological Drug Products Using Dermatopharmacokinetics
Improved Bioequivalence Assessment of Topical Dermatological Drug Products Using Dermatopharmacokinetics
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DOI：
10.1007/s11095-008-9742-9
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发表时间：
2009-02-01
影响因子：
3.7
通讯作者：
Bunge, Annette L.
中科院分区：
文献类型：
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作者：
N'Dri-Stempfer, Berthe;Navidi, William C.;Bunge, Annette L.
目的.已考虑采用皮肤药代动力学（DPK）方法对局部生物利用度进行比较评估，在该方法中，使用胶带条采样在人体体内测量角质层（SC）中的药物水平，作为应用后和移除产品后时间的函数。迄今为止，其应用受到相互矛盾的结果的限制，并担心该方法的可变性需要大量的治疗部位和志愿者。本研究的目的是测试是否修订后的协议可以更好地评估生物等效性。对三种1%硝酸益康唑乳膏产品（SC为作用部位）进行了盲法研究，以检查DPK方法的几种修改。除了旨在减少实验变异性的方案变更外，还在每个受试者中重复测量一次摄取时间和一次清除时间来评估生物等效性。在14名志愿者中，每种产品仅用4个治疗部位就可以得出生物等效性的结论，这一数量不到以前DPK研究所需数量的三分之一。可以在较少的受试者中使用较少的治疗部位，采用对实验室间差异不太敏感的稳健方法，最终评估比较生物等效性。
Purpose. A dermatopharmacokinetic (DPK) approach, in which drug levels in the stratum corneum (SC) are measured as a function of time post-application and post-removal of the product using tape-strip sampling in vivo in humans, has been considered for the comparative assessment of topical bioavailability. Its application to-date has been limited by contradictory results and concerns that variability in the method necessitates large numbers of treatment sites and volunteers. The objective of this study was to test whether a revised protocol could better assess bioequivalence.Methods. A blinded study of three 1% econazole nitrate cream products, for which the SC is the site of action, was conducted to examine several modifications to the DPK methodology. In addition to protocol changes designed to reduce experimental variability, bioequivalence was assessed at a single uptake time and a single clearance time measured in duplicate in each subject.Results. Conclusive determinations of bioequivalence were achieved with only four treatment sites per product in each of 14 volunteers, which was less than one-third the number required in a previous DPK investigation.Conclusions. Comparative bioequivalence can be assessed conclusively with fewer treatment sites in fewer subjects with robust methods that should be less sensitive to inter-laboratory differences.