Dermatopharmacokinetics

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. 

A further bias in determining dermatopharmacokinetics may originate from imprecise repetitive application of the tape on the skin being stripped. The use of a thin template to delimit the skin area is a simple way to keep the tape stripping area constant and unchanged during the entire tape stripping procedure. 

A further factor influencing dermatopharmacokinetics is the duration of tape stripping procedure. Redistribution of the solute in the SC may occur when tape stripping procedure is performed over a long period of time relative to its lag time for diffusion across SC.15 Furthermore, lateral spreading of the solute from neighboring, noninvolved skin into the stripped area may happen under certain circumstances.16... 

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]. 

Fig. 9 Idealized dermatopharmacokinetic profile for a topically applied compound illustrating uptake and elimination phases. The amount of drug in the stratum corneum is determined by summing the total amount removed by tape stripping at each time interval.

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. 

Pershing, L.K. Dermatopharmacokinetics for assessing bioequivalence of topically applied products in human skin. Cosmet. Toiletries 2000, 115 (5), 43-51. 

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. 

Some dermatopharmacokinetic models attempt to develop linkages between chemical concentrations in a specific compartment with a... 

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. 

Williams, P.L. and Riviere, J.E., 1995, A biophysically-based dermatopharmacokinetic compartment model for quantifying percutaneous penetration and absorption of topically applied agents. I. Theory, J. Pharm. Sci., 84 599-608. 

Dary, C.C., Blancato, J.N., and Saleh, M.A., 2001, Chemomorphic analysis of malathion in skin layers of the rat implications for the use of dermatopharmacokinetic tapestripping in exposure assessment to pesticides, Reg. Toxicol. Pharmacol, 34, 234-248. 

Wester, R.C. and Maibach, H.I. (1986). Dermatopharmacokinetics a dead membrane or a complex multifunctional viable process in J.W. Bridges and L.P. Chasseaud (eds.). Progress in Drug Metabolism, London Taylor and Brands, pp. 95-109. 

Zhai H, Maibach HI (1996) Percutaneous penetration (Dermatopharmacokinetics) in evaluating barrier creams. In Eisner P, Lachapelle JM, Wahlberg JE, Maibach HI (eds) Prevention of contact dermatitis. (Curr Probl Dermatol) Karger, Basel, pp 193-205... 

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