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Partitioning, Diffusivity and Clearance of Skin Permeants in Mammalian Dermis



Details

  • Personal Author:
  • Description:
    The partition coefficients (K(de)) and diffusivities (D(de)) of compounds in mammalian dermis were examined through an analysis of in vitro permeation data obtained from the literature combined with experimental results with the test permeant, (3)H-testosterone. The literature data involved 26 compounds ranging in molecular weight from 18 to 476 Da and four species-human, guinea pig, rat and mouse. Testosterone was studied by permeation and desorption measurements employing excised human dermis in the presence and absence of external serum albumin. Mathematical models for both K(de) and D(de) were developed. The K(de) model involved ionization, binding to extravascular serum proteins and partitioning into a small lipid compartment. The D(de) model employed a free diffusivity with a liquid-like size dependence multiplied by a binding factor derived from K(de). An additional analysis considered in vivo dermal concentration profiles of topically applied permeants. Literature data for 5 of 6 permeants were shown to be well described by a previously published model for capillary clearance in the dermis, which leads to an exponential decay of concentration with depth. Computed decay lengths (1/e values) ranged from 210 to 920 microm, and the corresponding clearance rate constants k(de) ranged from 0.9 x 10(-4) to 14 x 10(-4)s(-1) (n=8). Departures from the exponential decay profile are discussed in terms of non-uniform capillary clearance and incomplete attainment of a steady-state. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    0378-5173
  • Document Type:
    Text
  • Funding:
    Grant
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Pages in Document:
    64-79
  • Volume:
    346
  • Issue:
    1
  • NIOSHTIC Number:
    nn:20033027
  • Citation:
    Int J Pharm 2008 Jan; 346(1-2):64-79
  • Contact Point Address:
    Gerald Kasting, College of Pharmacy, University of Cincinnati Academic Health Center, P.O. Box 670004, Cincinnati, OH 45267-0004
  • Email:
    Gerald.Kasting@uc.edu
  • Federal Fiscal Year:
    2008
  • Performing Organization:
    University of Cincinnati
  • Peer Reviewed:
    True
  • Start Date:
    20020901
  • Source Full Name:
    International Journal of Pharmaceutics
  • End Date:
    20130731
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:0c24a067a61d4995ab0e95ba8411a06de57313290eb899143d610544d5eee24cbf763f2f4b811da92d4c6a3bda216eb981469db40173502d109466db35108958
  • Download URL:
  • File Type:
    Filetype[PDF - 597.35 KB ]
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