C. Lotte

Regional variation in percutaneous absorption in man: measurement by the stripping method

SummaryThe influence of anatomic site on the relationship between total penetration of a molecule and its quantities present in the stratum corneum (SC) 30 min after application was quantified in an in vivo study. For each site, six male volunteers received two symmetrical applications of 1,000 nmol benzoic acid 14C to an area of 1 cm2 for 30 min. The first application permitted measurement of total absorption of benzoic acid within 4 days (urinary excretion method), while the second enabled determination of the quantity of benzoic acid in the SC at the end of the application time. Total penetration according to site is: back < arm < chest < thigh < abdomen < forehead, (with the forehead being three times more permeable than the back). Whatever the sites and the origin of the differences observed, the results show that the single measurement of the amounts of a compound present in the SC at 30 min postapplication appears sufficient to predict its total penetration, these two parameters being linearly correlated (r=0.97, P<0.001).

In vivo relationship between transepidermal water loss and percutaneous penetration of some organic compounds in man: effect of anatomic site

SummaryThe relationship between the percutaneous penetration of four chemicals and transepidermal water loss (TEWL) was investigated in vivo in man as a function of anatomic site. The findings showed an appreciable difference in the permeability of the skin from one site to another with regard to both water loss and chemical penetration. In addition, independent of the physicochemical properties of the molecules administered, there was a linear relationship between TEWL and penetration. These data confirm both the importance of anatomic site in the degree of permeability of the cutaneous barrier and the utility of determinations of TEWL and percutaneous absorption in the evaluation of its functional condition.

The measurement of the stratum corneum reservoir: a simple method to predict the influence of vehicles on in vivo percutaneous absorption

The influence of nine vehicles on in vivo percutaneous absorption of benzoic acid has been studied in the hairless rat. Although the vehicles used were simple in composition, the total amount of benzoic acid which penetrated varied by a factor of 50. A weak relationship was found between penetration of benzoic acid and its maximum solubility in the different vehicles. A linear relationship was demonstrated between the amount of benzoic acid present in the stratum corneum at the end of a 30 min application period and the total amount absorbed over 4 days. We suggest that the influence of a vehicle on the overall absorption of a substance can therefore be predicted by simply measuring the amount present in the stratum corneum at the end of a 30 min application period.

Racial differences in the in vivo percutaneous absorption of some organic compounds: a comparison between black, Caucasian and Asian subjects.

Individual differences exist between patients, and, for topical therapy, differences in skin due to race may be a consideration. Pharmacological response depends upon the percutaneous absorption and the inherent activity of the chemical once absorbed into the biological system. Our objective was to determine the in vivo percutaneous absorption of three test chemicals in human subjects with Asian (A), black (B) and Caucasian (C) ethnic skin. Following a 30 min topical application on the upper outer arm of 1 Μmol/cm214C-labeled chemical, percutaneous absorption was determined by both urinary excretion and the stripping technique. Amounts absorbed were: for benzoic acid 1.43 ± 0.27% (SD) (A), 1.07 ± 0.18% (B), 1.2 ± 0.19% (C); for caffeine 1.06 ± 0.17% (A), 1.01 ± 0.19% (B) and 0.96 ± 0.12% (C); for acetylsalicylic acid 1.8 ± 0.31% (A), 1.59 ± 0.31% (B) and 2.12 ± 0.36% (C). No statistical difference (P>0.05) was found in percutaneous absorption of benzoic acid, caffeine or acetylsalicylic acid between Asian, black and Caucasian subjects.

In vivo percutaneous absorption: a key role for stratum corneum/vehicle partitioning

SummaryPercutaneous absorption of five compounds was studied in the hairless rat in vivo: benzoic acid, caffeine, hydrocortisone, inulin and thiourea. The results clearly demonstrate that, as with in vitro experiments, a steady-state flux can be achieved in vivo. This steady-state flux is strongly molecule dependent. Thus, the values for inulin and benzoic acid differ by a factor of about 40. In contrast, although the physicochemical properties of the studied compounds vary widely, their lag times were not significantly different. The mean lag time was 11±2 min. Different compounds could be considered to have approximately the same apparent diffusion coefficient with regard to their percutaneous absorption in vivo. Thus, for a given thickness of stratum corneum and a given anatomical site, the penetration flux value of a substance depends only on its stratum corneum/vehicle partition coefficient. Using a classical model, we have demonstrated that the amount of substance present in the stratum corneum (Qsc) at equilibrium (30 min) is related to this partition coefficient. There is also a linear relationship between steady-state flux and Qsc. In practice, the in vivo steady-state flux of penetration of a compound can be predicted from the simple measurement of the amount present in the stratum corneum after a contact time of 30 min.

In vivo distribution of linoleic acid in hairless rat skin following topical administration

Deficiency of essential fatty acids (EFA) in humans leads to chronic squamous dermatosis [12]. Epidermal disorders (acanthosis, hyperkeratosis) [1, 5, 8, 10] and effects on mitotic activity and DNA synthesis in basal layers [5, 6, 8] have been described in EFA-deprived animals. Concomitant with these disorders, a large increase of transepidermal water loss (TEWL) has been reported, showing that the barrier function of the horny layer is also affected [8, 10]. EFA deficiency even has an impact on the other targets, such as sebaceous glands and capillaries in the dermis [10]. It has been shown that topical application of linoleic acid (LA) or its metabolites (Y LA, arachidonic acid) abolishes the effects of EFA deficiency [4, 11, 13, 17]. In EFA-deprived humans, topical application of LA tends to restore normal values in serum EFA, thus indicating the strong penetration of LA [9]. Furthermore, recent findings [2, 3] in hairless rats and in man have shown that topically applied LA or linoleic acid concentrates in epidermal and dermal tissues. In the study briefly reported here, we attempted to precisely locate the LA in cutaneous structures following topical application in vivo on the hairless rat. A 4-rag oil/water emulsion, containing 2% (w/w) U 14 C LA (140 nmol); New England Nuclear; specific activity 125 gCi/g emulsion, was applied to 2 cm 2 back skin of five Sprague-Dawley hairless rats. The rats weighed 230 _+ 20 g and had been anesthetized by i.p. injection of butyrolactone (0.5 ml/kg). At the end of the application time (4 h), the excess cream was wiped