Appropriate methodologies for the determination of drug penetration in diseased skin have not yet been established. The aim of this study was to determine the cutaneous penetration of a metronidazole cream formulation in atopic dermatitis, employing dermal microdialysis and tape strip sampling techniques. Non-invasive measuring methods were used for the quantification of the severity of the dermatitis. Skin thickness and the depth of the microdialysis probes in the skin were measured by 20 MHz ultrasound scanning. Metronidazole concentration, sampled by microdialysis, was 2.4-fold higher in the atopic dermatitis compared with uninvolved skin (p<0.001). Tape stripping methodology did not disclose this difference in penetration. Thus, the skin layer of interest and the integrity of the skin barrier should be considered when selecting sampling methodology. Microdialysis sampling is the method of choice whenever the dermis is the target tissue for topical treatment and a skin disease affecting the barrier function is present.
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.
Aim: To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence. Methods: Nine microdialysis probes were inserted in the volar aspect of the left forearm of 14 healthy volunteers and, following application of the 3 metronidazole creams, microdialysis samples were collected for 5 h. On the right forearm, tape strip sampling was performed 30 and 120 min after product application. At the end of the experiment, ultrasound scanning measurements confirmed that all probes were placed inside the dermis. Results: There was no statistical difference in penetration of the 3 topicals as determined by microdialysis. However, their bioequivalence could not be determined due to intersubject variability exceeding the criteria for bioequivalence evaluation. Tape strip sampling established a bioequivalence between 2 of the creams, but rejected any bioequivalence between these 2 formulations and the third. The third formulation was a generic formulation approved despite containing a lower concentration of metronidazole (0.75%) than the innovator formulation (1.0%). The result of the bioequivalence evaluation depends on the methodology employed. Conclusion: Whenever the dermis is the target tissue, microdialysis provides the most relevant information on drug bioavailability.
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