Pharmacokinetics

The stratum corneum (superficial keratin layer) is both the principal barrier to penetration of drugs into the skin and a reservoir for drugs; a corticosteroid may be detectable even 4 weeks after a single application.

Drugs are presented in vehicles, e.g. cream, ointment, and their entry into the skin is determined by the:

• rate of diffusion of drug from the vehicle to the surface of the skin (this depends on the type of vehicle, see below)

• partitioning of the drug between the vehicle and the stratum corneum (a physicochemical feature of the individual drug) and

• degree of hydration of the stratum corneum (hydration reduces resistance to diffusion of drug).

Vehicles (bases1) are designed to vary in the extent to which they increase the hydration of the stratum corneum; e.g. oil-in-water creams promote hydration (see below). Some vehicles also contain substances intended to enhance penetration, e.g. squalane (p. 306).

Absorption through normal skin varies with site; from the sole of the foot and the palm of the hand it is relatively low, it increases progressively on the forearm, the scalp, the face until on the scrotum and vulva absorption is very high.

Where the skin is damaged by inflammation, burn or exfoliation, absorption is further increased.

If an occlusive dressing (impermeable plastic membrane) is used, absorption increases by as much as 10-fold (plastic pants for babies are occlusive, and some ointments are partially occlusive). Serious systemic toxicity can result from use of occlusive dressing over large areas.

A drug readily diffuses from the stratum corneum into the epidermis and then into the dermis, where

1 The chief ingredient of a mixture.

it enters the capillary microcirculation of the skin, and thus the systemic circulation. There may be a degree of presystemic (first-pass) metabolism in the epidermis and dermis, a desirable feature to the extent that it limits systemic effects.

Transdermal delivery systems are now used to administer drugs via the skin for systemic effect (see p. 109).

Topical preparations

It is convenient to think of these under the following headings:

• Vehicles for presenting drugs to the skin

• Emollients, barrier preparations and dusting powders

• Topical analgesics

• Antipruritics

• Adrenocortical steroids

• Sunscreens

• Miscellaneous substances.

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