Improved Method for Determining Partition and Diffusion Coefficients in Human Dermis

Details

• Personal Author:
  Ibrahim R ; Kasting GB
• Description:
  Accurate values of partition and diffusion coefficients within the lower skin layers are among the information required to estimate skin concentrations of permeants following topical application. For highly lipophilic compounds these parameters also play a significant role in determining systemic absorption rates. In this study methodology is described for making more accurate in vitro measurements of partition and diffusion coefficients in dermis. Isolated human dermis obtained from surgical reduction was mounted in side-by-side diffusion cells in the presence and absence of a dialysis membrane (5000 MW cut-off) placed between the dermis and the donor solution. Permeation of N,N-diethyltoluamide (DEET) and diclofenac across the composite membrane system, as well as steady-state skin concentrations, were measured by radiochemical techniques. For the highly protein bound compound, diclofenac, dermis permeability, and partition coefficient determined in the presence of the dialysis membrane were significantly higher than those determined in its absence. No significant differences were observed for the moderately protein bound DEET. The results show that, in the absence of a stratum corneum barrier, attention must be given to the diffusion of soluble proteins in order to obtain accurate estimates of transport and partitioning parameters for highly protein bound solutes in dermis. [Description provided by NIOSH]
• Subjects:
  Insecticides Occupational Health Safety Skin Skin Absorption
• Keywords:
  Author Keywords: Albumin DEET Dermal Absorption Diffusion Dose Response Drug Transport In Vitro Models Membrane Transport N,N-diethyl-meta-toluamide Passive Diffusion/Transport Permeability Pesticides And Agricultural Chemicals Protein Binding Skin Skin Absorption Skin Exposure Tissue Partition

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• ISSN:
  0022-3549
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  99
• Issue:
  12
• NIOSHTIC Number:
  nn:20056073
• Citation:
  J Pharm Sci 2010 Dec; 99(12):4928-4939
• Contact Point Address:
  Gerald B. Kasting, James L. Winkle College of Pharmacy, Academic Health Center, University of Cincinnati, Cincinnati, Ohio
• Email:
  gerald.kasting@uc.edu
• CAS Registry Number:
  N,N-Diethyl-m-toluamide (CAS RN 134-62-3)
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Manufacturing ; Agriculture, Forestry and Fishing
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20020901
• Source Full Name:
  Journal of Pharmaceutical Sciences
• End Date:
  20130731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:27c559d1030da0d43630a53f575054d993393622a302b0ec71f82a1a62f2751142b8ebdffb5caf0a3ecc7d936d2af595ed2e6033b3c2ee77f5b3b344bf53cf2f
• Download URL:
  https://stacks.cdc.gov/view/cdc/213762/cdc_213762_DS1.pdf
• File Type:
  [PDF - 217.47 KB ]