Human autopsy skin was sliced into three sections; an outer epidermis-rich layer, a middle dermis layer, and an inner dermis and subcutaneous fat layer. Each slice was bathed in lindane solutions over a 50-fold concentration range for 48 h at 37 degrees C. Lindane uptake by the skin was extensive (less than 90%) for all concentrations and all skin slices. Equilibrium dialysis with lindane at 37 degrees C for 24 h showed binding affinities by the skin sections to exceed 98%. The binding constants of the outer skin section (epidermis-rich) were higher than those of the middle and inner sections. The binding attraction for lindane by United States Pharmacopeia (USP) human plasma protein fraction (mean 90.5% bound) resulted in its competitive extraction from the skin slices in a three-compartment dialytic procedure. Since the least binding constants were in the middle and inner layers, and since lindane has a preference for plasma over skin, the two (inner skin and plasma) may combine to create the sink conditions necessary for lindane percutaneous absorption into the body. This plus the high epidermis capacity for lindane explains why in some instances (such as occlusion) high levels of lindane can be percutaneously absorbed.

Biological Transport, Active↗

PubMed1983

[Non-approved anti-obesity drug combinations and products].

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Drug Combinations↗

PubMed1983

Percutaneous penetration of hydrocortisone in humans following skin delipidization by 1:1:1 trichloroethane.

The effect of skin delipidization in humans on the percutaneous penetration of hydrocortisone was investigated in a cross-over trial. The delipidizing agent was 1:1:1 trichloroethane, a common industrial organic solvent. The findings do not show any significant difference in the topical absorption of hydrocortisone with and without skin delipidization. It was postulated that the natural skin barrier was reestablished by the metabolic cutaneous lipid regeneration concomitant with the absorption of the fatty ingredients from the cream.

Adult↗

PubMed1983

Malathion binding to sections of human skin: skin capacity and isotherm determinations.

Human autopsy skin was sliced into three sections: an outer epidermis-rich layer, a middle dermis layer, and an inner dermis and subcutaneous fat layer. Each skin slice was bathed in malathion solutions over a 100-fold concentration range of 0.02-3.0 microM/g skin for 48 h at 37 degrees C. Malathion uptake approximated 50% for each skin layer over the total concentration range. Skin capacity for malathion is thus large. Single and double compartment dialysis was used to determine free and bound malathion. Isotherm calculations gave a partition coefficient intercept for epidermis-rich and dermis tissues with aqueous buffer of 2.72 and 2.74, respectively. That of the inner layer of skin was less at 1.70. When malathion was dialyzed against simulated plasma, the binding decreased 2-fold. Since the least partition coefficient (less bound malathion) was in the inner layer of skin, and since malathion has a preference for plasma over water, the two (inner skin and plasma) may combine to create the sink conditions necessary for malathion percutaneous absorption into the body.

Binding Sites↗

PubMed1978

pH effect on the percutaneous penetration of lignocaine hydrochloride.

(1) The percutaneous penetration of lignocaine hydrochloride is affected in vitro by the pH; alkalinity increased the portion of the unionized drug which permeated through the lipoid outer skin membrane of guinea pigs. (2) The amount of lignocaine accumulated on the dermal side of the diffusion cell containing isotonic phosphate buffer (pH 7.4) was directly proportional to the initial concentration of the applied drug at the alkaline pH. (3) The dermal transfer rates of lignocaine into the isotonic phosphate buffer (pH 7.4) of the diffusion cell decreased with the increase in the pH of the initially applied solution on the epidermal side of the diffusion cell; the simultaneous cutaneous penetration of the alkaline buffer promoted retention of the unionized drug in the dermis. (4) Percutaneous penetration of lignocaine hydrochloride represents a dual-stage process involving dissimilar rates of clearance into cutaneous tissue and transfer from dermis to body fluids. Variations in the alkaline pH of lignocaine hydrochloride solution appear to govern the rate-limiting factor of the total percutaneous penetration; the pharmacologic action of lignocaine may thus be localized.

Animals↗

PubMed1977

Comparative subcutaneous absorption of local anesthetics: lidocaine, procaine and tetracaine.

The pH partition hypothesis was applied to the absorption of ionizable local anesthetic amines through the subcutaneous (s.c.) route. Solutions of lidocaine hydrochloride (LHCl), procaine hydrochloride (PHCl) and tetracaine hydrochloride (THCl) at various pH were implanted on s.c. animal tissue through a glass absorption cell. The s.c. absorption of these drugs was evaluated from the clearances' slopes evolved by determination of the drugs' concentrations in the cell at definite intervals. The higher the pH level, these conjugated bases become more unionized and lipid partitioned resulting in increased rates of s.c. absorption. The extent of unionization is governed by the pka of each of these drugs; at the high feasible pH--procaine which is least unionized--its s.c. absorption rate is nearly a third of that of lidocaine or tetracaine. The pH effect on s.c. absorption of local anesthetics was substantiated by estimation of lethal time50 (LT50) in mice.

Animals↗

PubMed1972