Assessment of cutaneous drug delivery using microdialysis.
During the last decade microdialysis has been successfully applied to assess cutaneous drug delivery of numerous substances, indicating the large potential for bioequivalence/bioavailability evaluation of topical formulations. The technique has been shown to be minimally invasive and supply pharmacokinetic information directly in the target organ for cutaneous drug delivery with high temporal resolution without further intervention with the tissue after implantation. However, there are a few challenges that need to be addressed before microdialysis can be regarded as a generally applicable routine technique for cutaneous drug delivery assessments. Firstly, the technique is currently not suitable for sampling of highly lipophilic compounds and, secondly, more studies are desirable for elucidation of the variables associated with the technique to increase reproducibility. The present literature indicates that the condition of the skin at the individual assessment sites is the main variable, but also variables associated with relative recovery, differentiation between the pharmacokinetic parameters (i.e., lag time, distribution, absorption and elimination rate) can influences the reproducibility of the technique. Furthermore, it has been indicated that cutaneous microdialysis in rats may be useful for prediction of dermal pharmacokinetic properties of novel drugs/topical formulations in man.
Kreilgaard
Mads
M
Department of Neurochemistry and Discovery ADME, H Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, Denmark. makr@lundbeck.com
D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D010599:Pharmacokinetics; D015203:Reproducibility of Results; D012867:Skin / Q000737:chemistry / Q000378:metabolism; D012869:Skin Absorption; D013810:Therapeutic Equivalency; D013997:Time Factors; D014018:Tissue Distribution