Dermatopharmacokinetic studies

The study design is dependent on the nature of the active drug. The bioequivalence study can be a comparative skin blanching study as in glucocorticoids (FDA, Topical Dermatological Corticosteroids In Vivo Bioequivalence, June 2,1995.) or a comparative clinical trial or any other appropriate vahdated bioequivalence study (e.g., dermatopharmacokinetic study) for the topical dermatological drug product. 

Following tape stripping, when performing dermatopharmacokinetic studies, the solute contained in the SC removed by tape strips is extracted and measured using appropriate analytical methods such as HPLC. 

Despite the simplicity of tape stripping procedure, numerous artifacts may result in inaccurate conclusions following dermatopharmacokinetic studies. The origin of such artifacts as well as possible ways to avoid them are discussed in the following. 

In Vivo Bioequivalence Studies In vivo studies are conducted to establish the biological availability or activity of the drug from a topically applied semisolid formulation. Dermatopharmacokinetic studies, pharmacodynamic studies, or comparative clinical trials are generally conducted to assess the bioequivalence of topical products [16,17]. 

Other concerns have been expressed. ° These include the observation that vehicle components of the products to be evaluated may have different effects on the adhesive properties of the tape. In addition, it is important to appreciate that because the dermatopharmacokinetic bioequivalence studies will most likely be carried out on normal disease-free human volunteers, the generated data may show little resemblance to the actual drug distribution within the stratum corneum of patients. Non-etheless, following further validation, the technique will have several advantages. For example, basic pharmacokinetic parameters, such as AUC, Craax, max, Tud half-Hfc, may be approximated from the data obtained. In addition, the approach could be applicable to all types of topical preparation. 

The primary purpose for most dermatopharmacokinetic models is to quantitate the linkage between anatomical and physiological properties of skin that play rate-limiting roles in absorption with target sites for which concentrationtime profiles are needed. The complexity of the models is a function of the chemical being studied as well as the level of precision (concentration, time frame) required for the prediction. For example, models created to estimate total percent dose absorbed are much simpler than those designed to predict the time and magnitude of peak plasma concentrations in a subject. 

Chang, S.K., Williams, P.L., Dauterman, W.C., and Riviere, J.E., 1994, Percutaneous absorption, dermatopharmacokinetics, and related biotransformation studies of carbaryl, lindane, malathion and parathion in isolated perfused porcine skin. Toxicology, 91 269-280. 

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