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Biomedical subjects

A Zesch

Publications and source records attributed to A Zesch.

At least 37 records · Page 2Linked to original sources
PubMed1981

[On interactions of drugs on and in the skin/comparative studies on the mutual influences of ethyleneglycol-monosalicylate and benzylnicotinate (author's transl)].

Three radioactively marked substances (on the basis of a carbopol gel, 80% water - isopropanol) were analyzed comparatively in regard to the penetration of ethyleneglycolmonosalicylate and benzylnicotinate to intact and impaired human skin. The objective of the in-vitro study was to gain evidence on possible interaction of the locally applied substances upon skin penetration. Only 5 h after application ethyleneglycolmonosalicylate reaches a steady state of concentration in the corium of approximately 700-800 mumol/l tissue which is maintained (in contrast to nicotinate) even after 16 h exposure time. Benzylnicotinate reaches its maximum concentration (100-200 mumol/l tissue in all living layers of the skin) 100-300 min after application. After simultaneous local application of both substances the penetration of ethyleneglycolmonosalicylate in corium and subcutis is clearly intensified by benzylnicotinate. Substance distribution in skin cross section and kinetics do not change. Penetration of benzylnicotinate however, is delayed by the salicylate (especially at exposure time of 100-300 min). Results of comparative penetration studies with inverted skin (inverse penetration), intact and impaired (stripped) skin allow the following conclusion: penetration limiting of salicylate occurs in the horny layer only due to the optimal liberation. Penetration of nicotinate on the other hand, is already prevented "before" the skin because of insufficient liberation from the vehicle.

Drug Interactions↗
PubMed1979

The quantitative distribution of percutaneously applied caffeine in the human skin.

The distribution coefficient of caffeine (water/n-Octanol) and the estimation of caffeine in urine after local application indicate to a high permeation rate of caffeine through the skin. This could be confirmed by using different vehicles in vivo and in vitro. 14C labeled caffeine penetrates rapidly the epidermis and corium. The maximum of absorption is reached at 100 min after local application in vivo. In vitro by absence of the transport possibilities of blood and lymph vessels, the concentration at 1,000 min after local application is 450 X higher than in vivo. Therefore, after 1,000 min in vivo the concentration of caffeine in the different skin layers is very low.

Administration, Topical↗
PubMed1978

Quantitative determination of percutaneous absorption of radiolabeled drugs in vitro and in vivo by human skin.

We have measured concentrations of about 30 drugs in the living layers of the skin under conditions which provide data which are applicable in therapeutic treatment. Since the skin is a thin organ and small amounts of drug represent high target concentrations, it is necessary to select a sensitive quantitative method; observation of the kinetics of absorption using radiolabeled drugs is the method of choice. Because of possible hazards--and legal and ethical problems--absorption studies in human skin are commonly performed in vitro. Related in vivo investigations demonstrate the relevance and the limitations of the in vitro experiments. The main hindrance against penetration of drugs is by the horny layer. The barrier-function of this layer--if it is undisturbed--may be described by a multilayer model. The reciprocal function, the reservoir function, is important for the efficiency of topical treatment; it also plays a role in determining the unique pharmacokinetics of drug absorption in the skin and percutaneous resorption. If the horny layer is injured, i.e. in diseased skin, both the barrier and the reservoir functions are disturbed. In consequence, drug concentrations in the skin--and percutaneous resorption--may be greatly enhanced, and topically applied drugs may enter preferentially into diseased areas. The form of application, such as ointment, solution, etc. influences the penetration kinetics in such a specific manner that a specific vehicle for a specific drug should always be postulated. The frequently discussed hazards of side effects due to percutaneous resorption of drugs like corticosteroids are a function of the treated area rather than of its penetration capacity. Thus the indication for local or oral treatment of severe dermatoses should be considered in terms of the affected area. The relatively frequent side effects in the skin itself which originate from unnecessarily high drug concentrations and long term treatment must also be taken into account.

Administration, Topical↗
PubMed1977

Penetration, permeation, and absorption of triamcinolone acetonide in normal and psoriatic skin.

Penetration studies of radiolabelled Triamcinolone acetonide from ointment or cream preparations revealed that in cases of normal as well as psoriatic skin 70-90% of the applied substance remains on the surface. Normal horny layer stores up to 30% of the steroid. Nevertheless, a rapid penetration into the living layers of the skin is observed, whereby the epidermal concentrations reach levels between 5-10(-6) and 3-10(-5) M (mol per liter of tissue). The excretion in the urine took more than 72 h after removal of the excess of substance from the skin. In psoriatic skin, the epidermal and dermal concentrations were 3-10 times higher than in normal skin. This increase lies in the same range as the one resulting from removal of the horny layer by stripping prior to the application, as reported earlier.

Absorption↗
PubMed1977

Hydrocortisone (cortisol) concentration and penetration gradient.

Hydrocortisone (Cortisol) was incorporated into four different ointments at four concentrations (0.1% 0.3%, 1%, and 3%) and the amounts of the drug penetrating from these preparations into the different layers of excised skin were investigated. The effect of removing the horny layer on the penetration was also determined. Below a level of 1% ointments with intact horny layer and 0.3% with removed layer, a change in the ointment concentration alters the tissue concentration in the ratio 1:1. Above this level doubling of the concentration in the ointments causes an increase of tissue concentrations of only 20-50%. The removal of the horny layer increases the dermal concentrations 100 fold at each ointment concentration. Furthermore, a vasoconstriction test was performed with the different ointments. An increase in the concentrations above the 1% level failed to increase the effect on the vascular system of the skin. The in vitro and in vivo results are discussed with respect to the consequences on affected skin and the therapeutic efficacy of steroid preparations of different concentrations.

Administration, Topical↗
PubMed1976

[Penetrations kinetics and distribution of topically applied estrogens (author's transl)].

The penetration into the single layers of human skin in vitro of 17 alpha-estradiol, 17 beta-estradiol and estriol was investigated. The radiolabeled substances were incorporated into 4 standard ointments and into an alcoholic solution mixture. After application to the skin and after different penetration periods, the horny layer was taken off by adhesive tape stripping. The epidermis and the dermis were separated by slicing them down parallel to the skin surface in a freeze microtome. In each single layer, the amount of substance was determined and calculated relative to the applied quantity and in absolute concentrations (mug per tissue weight and molarity). Besides the expected dependence of the penetration on the type of ointment, there is a distinct dependence on the chemical structure: estriol penetrates considerably slower and in less concentrations into the living layers of the human skin than the estradiols. Furthermore, estriol reaches the dermis only in low concentrations so that this substance may be termed epidermotropic. 17 alpha-estriol which has only weak sexhormone properties in humans penetrates as well as the sexhormone 17 beta-estradiol.

Administration, Topical↗
PubMed1976

Penetration, permeation, and resorption of 8-methoxypsoralen. Comperative in vitro and in vivo studies after topical application of four standard preparations.

The penetration, permeation, and resorption of radioactively labelled 8-Methoxypsoralen was investigated in human skin. Siultaneously, the effects to time and ointment carrier on the penetration kinetics were ascertained. The carriers tested were: vaseline, aqueous wool-wax alcohol ointment, aqueous hydrophilic ointment and polyethylene glycol ointment. The absolute concentrations of 8-Methoxypsoralen were estimated in the horny layer, epidermis and dermis. With the most advantageous carrier, aqueous wool-wax alcohol ointment, 4-6X10(-5) M and 10(-5) M were attained in the epidermis and dermis, respectively. Moreover, it was shown that the substance penetrates rapidly (10 min) into the epidermis and dermis and the high concentrations reached constant over a period of 16 h. Only with a formulation of aqueous wool-wax alcohols is any accumulation at all achieved in the deeper areas of the horny layer. A uniform decrease in drug concentration with increasing depth of the horny layer is found with the other 3 vehicles, whereby slight variations in concentrations pertain from carrier to carrier. 4 h after local application, 8-Methoxypsoralen can be detected in the urine. Regardless of the ointment base employed, 8-Methoxypsoralen is no longer detectable in the urine 40 h after application. In comparison to the oral therapy, the same magnitude of percutaneous resorption into the central compartment is to be derived from the data, if half the body surface is treated locally.

Administration, Topical↗
PubMed1976

[Penetration, permeation and resorption of heparin. In vivo studies on human skin].

The penetration and permeation of radioactive heparin into human skin was investigated as well as absorption and excretion. Heparin concentrations and vehicles were those that are in common use in practical therapy. It was shown that in spite of its high molecular weight, heparin can penetrate through the intact horny layer barrier. The concentration of heparin found in the skin, e.g. 10 I.U./ml in the epidermis and 0.6 I.U./ml in the corium are biologically relevant and are expected to be able to exert an influence. The penetration rates have shown a clear dependence on the kind of vehicle.

Heparin↗
PubMed1975

[Penetration of radioactive hydrocortisone in human skin from various ointment bases. II. In vivo-experiments (author's transl)].

Absolute concentrations in the horny layer, epidermis, and dermis of therapeutical doses of topically applied hydrocortisone to human skin (in vivo) are reported. Using vaseline as vehicle 2-10(-4) molar concentrations are found in the epidermis and 3-10(-5) molar concentrations in the dermis. Further, three vehicles revealed minor concentrations. Comparison of the results with similar in vitro-investigations, reported earlier, allow to judge the resorption rate by the intact capillary system. Uptake of hydrocortisone by the vessels is observed. With high rates of penetration vasoconstriction seems to limit the resorption, while this is not the case with low rates, for instance with polyethyleneglycol as vehicle. Thus a differing drug liberation from the vehicle causes qualitatively different permeation kinetics. The elimination by urine, however, was practically the same. It is concluded that different vehicles may cause different therapeutic concentrations of the drug in the skin, but equal systemic side effects.

Administration, Topical↗
PubMed1975

Absolute concentrations of dithranol and triacetyl-dithranol in the skin layers after local treatment: in vivo investigations with four different types of pharmaceutical vehicles.

The pharmacokinetics of dithranol (anthralin) and its triacetate were investigated by employing a method which determines the quantity of the drug that penetrated into single layers of the human skin in vivo. For this purpose, tritium-labeled dithranol or triacetyl-dithranol was incorporated into four different ointments. The ointments were applied to the skin and biopsies were taken after 10, 30, 100, and 1000 min. The horny layer was removed before biopsy by Scotch tape stripping. The biopsies were sliced horizontally and the tritium determined in each sample. Dithranol as well as its triacetate penetrated best from more hydropholic ointments (Vaseline and aqueous wool-wax-alcohol ointment). From hydrophilic ointments (polyethylene glycol ointment and aqueous hydrophilic cream), only poor penetration was observed. Dithranol penetrated in far greater amounts than its triacetate, and the two compounds revealed fundamentally different penetration kinetics in epidermis and dermis. The data indicate that the triacetate was not split into its parent compound, dithranol, in substantial quantity, as the data obtained show the criteria of two independent substances.

Adult↗