Theoretical Analysis of the Effect of Cutaneous Metabolism on Skin Permeation of Parabens Based on a Two-Layer Skin Diffusion/Metabolism Model

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概要

• 論文の詳細を見る

• The effect of cutaneous metabolism on the skin penetration of drugs was analyzed based on a two-layer skin difusion/metabolism mode. In vitro permeation studies of propylparaben and butylparaben with or without an esterase inhibitor, diisopropyl fluorophosphate (DFP), were performed. Pretreatment of the skin with DFP prolonged the lag time for the penetration of intact parabens. Additionally, DFP signifidcantly decreased the total flux of butylparaben, but not that of propylparaben. Model analysis of the penetration profiles revealed that DFP inhibits the cutaneous metabolism without affecting any other processes. To comprehensively understand the relationships among lipophilicity, metabolic rate, and skin permeation of drugs, simulation studies were performed with newly derived equations concerning the permeability coefficient and the lag time for the penetration of both intact and metabolite forms. The analysis revealed that the lag time for the penetration of both intact and metabolite forms becomes shorter with increasing metabolic rate. As the metabolic rate of the drug increases, skin penetration of the intact form decreases whereas that of the metabolite increases. The total flux of intact and metabolite forms increases with increasing metabolic rate, being more obvious for highly lipophilic drugs. This indicates that the permeation of lipophilic compounds such as butylparaben is more highly affected by cutaneous metabolism in the viable layer because these compounds easily penetrate the stratum corneum layer. Consequently, the balance between the permeability of drug across the stratum corneum and the dermis has been implicated to impose a significant influence on the percutaneous absorption of drugs subjected to cutaneous metabolism.

• 社団法人日本薬学会の論文
• 1999-03-15

著者

• Yamashita Fumiyoshi

  第一三共 葛西研究開発センター

• Yamashita Fumiyoshi

  Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University

• Yamashita Fumiyoshi

  Departments Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University

• Yamashita Fumiyoshi

  Graduate School Of Pharmaceutical Sciences Kyoto University

• Hashida Mitsuru

  Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University

• Hashida Mitsuru

  京都大学 薬学研究科病態情報薬学

• Hashida Mitsuru

  Dep. Of Drug Delivery Res. Graduate School Of Pharmaceutical Sciences Kyoto Univ. 46-29 Yoshidashimo

• Hashida Mitsuru

  Inst. Of Integrated Cell-material Sciences (icems) Kyoto Univ.

• Yamashita Fumiyoshi

  Dep. Of Drug Delivery Res. Graduate School Of Pharmaceutical Sciences Kyoto Univ. 46-29 Yoshidashimo

• Hashida M

  Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University

• Hashida Mitsuru

  Graduate School Of Pharmaceutical Sciences Kyoto University

• LIM Chee

  Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University

• YAMASHITA Fumiyoshi

  京大院薬

• HASHIDA Mitsuru

  京大院薬

• SEKO Noritaka

  Department of Pharmaceutical Research, Nippon Boehringer Ingelheim Co., Ltd.

• BANDO Hiroto

  Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University

• Lim Chee

  Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University

• Lim Chee

  Department Of Automatic Control And Systems Engineering The University Of Sheffield

• Bando Hiroto

  Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University

• Seko Noritaka

  Department Of Pharmaceutical Research Nippon Boehringer Ingelheim Co. Ltd.

• Yamashita Fumiyoshi

  Dep. Of Drug Delivery Res. Graduate School Of Pharmaceutical Sciences Kyoto Univ.

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