Percutaneous absorption in experimental epidermal disease

Little is known about the absorption of topical drugs in epidermal disease associated with epidermal proliferation and altered keratinization. An abnormal hairless mouse epidermis was produced by three different methods: ultraviolet light irradiation, topical vitamin A acid and topical acetic acid. An increased epidermal thickness resulted and the in vitro percutaneous absorption of 0.1% (4-14C) hydrocortisone was found to be increased when compared with normal hairless mouse epidermis. This is evidence for defective skin barrier function in experimental epidermal disease.     

Percutaneous absorption in the aged

The work described in this article reveals a remarkable lack of consensus as to whether percutaneous absorption changes as humans grow older. The data that have been recorded point to possible significant alterations in the barrier function with age. The importance of these observations with respect to dermatopharmacology and dermatotoxicology is clear. The absence of a clearly defined relationship between aging, percutaneous penetration, and the properties of the molecules crossing the skin barrier represents an unacceptable gap in fundamental dermatologic knowledge. With the changing demographic pattern of Western civilization and the increasing awareness of human subjects for the condition of their skin, and the potential for drug delivery via their skin, it is crucial that we begin to establish precisely how the barrier function alters with increasing age. The answer to this question may permit unique improvements in the quality of both local and systemic health in aging populations.     

Histamine and epidermal proliferation

Histamine is liberated in the inflammatory reaction and has been reported to inhibit epidermal cell division in vitro. This study has investigated the eflFects of histamine and H1 and H2 antagonists on epidermopoiesis in vivo in man. No direct stimulatory effect of histamine was detected for normal epidermis. A combination of H1 antagonist (chlorpheniramine) and H2 antagonist (cimetidine) led to further increases in epidermal labelling indices in mitotically stimulated epidermis. The administration of H1 antagonist alone led to a decrease in mean epidermal thickness. These data suggest that histamine release is unlikely to play a major role in the hyperplasia of inflammatory dermatoses, but that it may be possible to influence epidermal reactions via the H1 and H2 receptors.     

Percutaneous absorption of minoxidil in man

The percutaneous absorption and excretion of 1% and 5% solutions of minoxidil labeled with carbon 14 were measured in 12 adult male subjects. These subjects were randomly assigned to the 1% and 5% minoxidil testing groups, and all received nine topical applications to a bald area on the scalp, with the radioactive solutions applied on days 1 and 9. Urinary excretion of radioactivity was low, with mean values ranging from 1.6% to 3.9% of applied dose. No radioactivity could be detected in fecal samples. Recovery of radioactivity from the skin surface and from scalp and pillowcase washes was in the range of 41% to 45% of applied dose. No adverse reactions or notable abnormalities were noted in the subjects during the study. Although minoxidil is poorly absorbed through the skin, systemic doses in the range of 2.4 to 5.4 mg/day can be anticipated if application is made to entire scalp.     

Percutaneous retinoid absorption and embryotoxicity

A single application of 17 micrograms/kg or 8.7 mg/kg all-trans-[10,11-3H2]-retinoic acid dissolved in acetone to shaved dorsal hamster skin resulted in rapid absorption and dose-dependent rates of elimination. An equation describing a two-compartment open model with a very brief lag time and first-order uptake and elimination was used to describe the central plasma compartment kinetics. Unchanged all-trans-retinoic acid represented less than or equal to 4% of the total circulating radio-activity. Peak circulating concentrations of parent all-trans-retinoic acid were less than those observed after an equivalent oral dose, but prolonged absorption from the skin appears to contribute to high total bioavailability of topical retinoid. Topical administration to intact skin of up to three consecutive doses of 10.5 mg/kg/d all-trans-retinoic acid or a single 5 mg/kg dose of etretinate (Ro 10-9359) during a critical stage of embryogenesis in hamsters caused erythema and/or dose-dependent epidermal hyperplasia at the site of application, but failed to induce a significant teratogenic response. Topical application of 0.01-1.0 mg/kg arotinoid Ro 13-6298 resulted in dose-dependent mucocutaneous toxicity and an increase in the numbers of dead embryos and malformed offspring. The marked skin toxicity and attenuated concentrations in maternal blood, compared to the oral route, limit the amounts of retinoid that can reach the hamster embryo. It is thus more important to compare the retinoid systemic values (absorbed dose) than it is to compare the oral or topical (applied) dose, when interpreting the results of conventional teratogenicity bioassays. The data suggest that in the human it is skin toxicity that limits the amounts of retinoid that can be applied and subsequently reach the embryo. In the rodent, overt skin toxicity under continued dosing could increase the amounts of retinoid penetrating the skin and reaching the embryo.     

Percutaneous absorption of organic sunscreens

The increased awareness of protection against skin cancer has led to a rise in the use of topically applied chemical sunscreen agents. There is a concern about the systemic absorption of organic filters in sunscreen formulations. The present study briefly reviews theoretical models for the prediction of the percutaneous penetration of the organic molecules and the accepted methods for the in vitro and in vivo evaluations of the penetration. The influence of the vehicle and the formulation viscosity on the penetration of sunscreens are examined. The development of novel methods for the minimization of sunscreen absorption is also discussed.     

Percutaneous absorption of azelaic acid in humans

Six healthy male volunteers received a single topical treatment with 5 g of an anti-acne cream containing 20% azelaic acid (AzA) onto the face, the chest and the upper back. One week later 1 g of AzA was given orally to the same subjects as aqueous microcrystalline suspension. Following the two treatments the renal excretion of the unchanged compound was measured. Analysis included ether extraction of the urine, derivatization of extract and HPLC with UV detection. After topical application 2.2 +/- 0.7%, and after oral administration 61.2 +/- 8.8% of the dose had been excreted unchanged with the urine. By comparing both amounts, the percutaneous absorption of AzA from the cream was assessed to 3.6% of the dermally applied dose.     

Percutaneous absorption of topically applied medication

Given the central role that topical medications play in treating skin disease, nurses must understand the delivery systems of topical preparations to make the most informed decisions for their patients and provide adequate patient education to ensure the best clinical outcomes.