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


CONCLUSIONS
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.
Department of Dermatology, Gentofte Hospital, 2900 Hellerup, Denmark. patriciagarcia@dadlnet.dk
Patricia García
PG
Ortiz
Steen Honoré
SH
Hansen
Vinod P
VP
Shah
Torkil
T
Menné
Eva
E
Benfeldt
D000279:Administration, Cutaneous; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D017453:Dermatitis, Irritant / Q000378:metabolism*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004890:Erythema / Q000139:chemically induced; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017551:Microdialysis / Q000379:methods; D008875:Middle Aged; D012867:Skin / Q000000981:diagnostic imaging / Q000293:injuries; D012869:Skin Absorption; D012967:Sodium Dodecyl Sulfate; D014463:Ultrasonography; D014870:Water Loss, Insensible
D003879:Dermatologic Agents; D008795:Metronidazole; D012967:Sodium Dodecyl Sulfate