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The effect of irritant dermatitis on cutaneous bioavailability of a metronidazole formulation, investigated by microdialysis and dermatopharmacokinetic method.

AbstractBACKGROUND:
Determination of drug penetration in diseased skin represents a challenge.
OBJECTIVE:
To compare dermal microdialysis and tape-strip sampling of drug penetration in normal skin and skin with irritant dermatitis.
METHODS:
The two methodologies were employed simultaneously in 16 healthy volunteers. Samples were collected in a study of the penetration of a metronidazole cream formulation (Flagyl 1%) applied to forearm skin in both areas with irritant dermatitis and normal skin. Barrier perturbation and the depth of microdialysis probes were quantified by non-invasive bioengineering methods.
RESULTS:
Microdialysis showed a significant threefold increase in metronidazole penetration in skin with irritant dermatitis compared with unmodified skin. Conversely, the concentration of metronidazole in tape-strip samples was significantly decreased in irritant dermatitis.
CONCLUSION:
The selection of sampling methodology should be based on the skin layer of interest as well as the integrity of the skin barrier. Whenever the dermal tissue is the target for topical treatment, microdialysis sampling should be the method of choice.
AuthorsPatricia García Ortiz, Steen Honoré Hansen, Vinod P Shah, Torkil Menné, Eva Benfeldt
JournalContact dermatitis (Contact Dermatitis) Vol. 59 Issue 1 Pg. 23-30 (Jul 2008) ISSN: 1600-0536 [Electronic] Denmark
PMID18537995 (Publication Type: Comparative Study, Evaluation Studies, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Dermatologic Agents
  • Metronidazole
  • Sodium Dodecyl Sulfate
Topics
  • Administration, Cutaneous
  • Adult
  • Analysis of Variance
  • Area Under Curve
  • Biological Availability
  • Dermatitis, Irritant (metabolism)
  • Dermatologic Agents (administration & dosage, pharmacokinetics)
  • Erythema (chemically induced)
  • Female
  • Humans
  • Linear Models
  • Male
  • Metronidazole (administration & dosage, pharmacokinetics)
  • Microdialysis (methods)
  • Middle Aged
  • Skin (injuries, ultrasonography)
  • Skin Absorption
  • Sodium Dodecyl Sulfate
  • Water Loss, Insensible

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