Pharmacokinetics at a Glance
- Compounds applied topically to the skin surface migrate along concentration gradients.
- The drug or its formulation may affect the skin barrier, resulting in time-dependent changes of the barrier function.
- There are significant regional variations in the barrier properties of the skin.
- Formulations differ in their physicochemical properties—this influences the kinetics of release and/or absorption and the onset, duration, and extent of a biologic response.
- The primary compartment that limits the percutaneous absorption of compounds is the stratum corneum.
- Diffusion within the viable tissue, as well as metabolism and resorption, also influence the bioavailability of compounds in specific skin compartments.
- Metabolic activity is a primary consideration in the design of prodrugs and may influence the bioavailability of drugs delivered via dermatologic or transdermal formulations.
Pharmacokinetics related to topical applications of drugs describes the time-dependent drug concentration following the application of the drug to the skin surface, its subsequent passage through the skin barrier into the underlying skin layers, and its distribution into the systemic circulation. The subject continues to hold the attention of research scientists and clinicians alike because of its relevance to dermatologic therapy and the possibility of topical application of current systemic medication that cannot be administered orally, such as peptides or proteins. However, this is an inherently complex subject, despite the advent of new insights into the principal factors that govern diffusion of a drug into and across the skin.
The major difficulty in developing an accurate description of the percutaneous absorption of a drug is related to the size of the compartments. A topical application of a cream or ointment is generally spread to a thickness of not greater than 10 μm. The thickness of the stratum corneum is also approximately10 μm, whereas the viable epidermis, dermis, and, to a greater extent, the systemic compartment, represent a large sink in which absorbed drugs undergo dilution to levels that often remain undetectable to all but the most sensitive techniques. The determination of the time-dependent changes in the concentration of a drug in individual compartments is technically challenging. After topical application of a drug formulation, several parameters can affect this process (Box 215-1).
Box 215-1 Parameters that Affect Drug Amounts in Skin Compartments |Favorite Table|Download (.pdf)
Box 215-1 Parameters that Affect Drug Amounts in Skin Compartments
- Formulations may undergo drastic changes in composition and structure.
- Drug or formulation may affect the skin barrier, resulting in time-dependent changes of the barrier function.
- Skin barrier may be affected by the type and progression of a disease.
- Regional variations in the barrier properties of the skin.
- Skin may respond to topical drug, enhancing or retarding percutaneous absorption.
- Metabolic capacity of skin may lead to exposure of skin or systemically to both parent drug and pharmacologically active metabolite(s).
Compounds applied topically to the ...