Kreilgaard Mads
Department of Neurochemistry and Discovery ADME, H Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, Denmark.
Adv Drug Deliv Rev. 2002 Nov 1;54 Suppl 1:S99-121. doi: 10.1016/s0169-409x(02)00117-5.
During the last decade microdialysis has been successfully applied to assess cutaneous drug delivery of numerous substances, indicating the large potential for bioequivalence/bioavailability evaluation of topical formulations. The technique has been shown to be minimally invasive and supply pharmacokinetic information directly in the target organ for cutaneous drug delivery with high temporal resolution without further intervention with the tissue after implantation. However, there are a few challenges that need to be addressed before microdialysis can be regarded as a generally applicable routine technique for cutaneous drug delivery assessments. Firstly, the technique is currently not suitable for sampling of highly lipophilic compounds and, secondly, more studies are desirable for elucidation of the variables associated with the technique to increase reproducibility. The present literature indicates that the condition of the skin at the individual assessment sites is the main variable, but also variables associated with relative recovery, differentiation between the pharmacokinetic parameters (i.e., lag time, distribution, absorption and elimination rate) can influences the reproducibility of the technique. Furthermore, it has been indicated that cutaneous microdialysis in rats may be useful for prediction of dermal pharmacokinetic properties of novel drugs/topical formulations in man.
在过去十年中,微透析已成功应用于评估多种物质的皮肤给药情况,这表明其在局部制剂生物等效性/生物利用度评估方面具有巨大潜力。该技术已被证明具有微创性,能够在植入后无需对组织进行进一步干预的情况下,以高时间分辨率直接在皮肤给药的靶器官中提供药代动力学信息。然而,在微透析可被视为一种普遍适用于皮肤给药评估的常规技术之前,仍有一些挑战需要解决。首先,该技术目前不适用于高度亲脂性化合物的采样;其次,需要更多研究来阐明与该技术相关的变量,以提高其重现性。现有文献表明,个体评估部位的皮肤状况是主要变量,但与相对回收率相关的变量以及药代动力学参数(即滞后时间、分布、吸收和消除速率)之间的差异也会影响该技术的重现性。此外,已有研究表明,大鼠的皮肤微透析可能有助于预测新型药物/局部制剂在人体中的皮肤药代动力学特性。