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Biomedical subjects

C Lotte

Publications and source records attributed to C Lotte.

16 recordsLinked to original sources
PubMed2002

Permeation and skin absorption: reproducibility of various industrial reconstructed human skin models.

Human reconstructed skin models could be very useful tools to quantify percutaneous permeation and absorption. Before using such models, the reproducibility in the same batch and/or various batches, i.e. the relevance of the results obtained, must be verified. The reproducibility of 3 industrial models--EpiDerm, Episkin and SkinEthic--was tested regarding the permeation and skin absorption of 3 topically applied compounds (with a large range of physicochemical properties): lauric acid, caffeine and mannitol. For all the models, the intrabatch reproducibility was greater than the interbatch reproducibility. According to the batches tested, the larger difference in terms of reproducibility between the 3 models was observed in the case of mannitol, a very poor permeant. In this case, the best reproducibility was observed with EpiDerm and Episkin. Moreover, the rank order of the 3 compounds applied, in terms of permeation and skin absorption, was the same as that expected from ex vivo human skin. Such results revealed human skin models as a promising means to test in vitro permeation and percutaneous absorption of topical products.

Drug Evaluation, Preclinical↗
PubMed1993

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 mumol/cm2 14C-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.

Adult↗
PubMed1991

Racial differences in corneocytes. A comparison between black, white and oriental skin.

It is well known that spontaneous desquamation and corneocyte size can reflect respectively stratum corneum cohesiveness and epidermal cell proliferation. The influence of skin pigmentation on these parameters has been investigated on the upper-outer arm of black, white and oriental volunteers, using the detergent scrub method. We found no difference between race in corneocyte surface area, a mean size of 900 microns 2 agreeing closely with that generally encountered in Whites on the upper-outer arm. By contrast, spontaneous desquamation is increased in black vis-à-vis white and oriental skin (factor 2.5, p less than 0.001). Taking into account the importance of the intercellular cement for the cohesion between corneocytes, racial differences in epidermal lipid composition should be investigated.

Adult↗
PubMed1990

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

Percutaneous 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.

Animals↗
PubMed1987

In vivo percutaneous penetration of some organic compounds related to anatomic site in humans: predictive assessment by the stripping method.

The effect of anatomic site on the in vivo relationship between the total penetration of four compounds and the amount of the compounds present in the stratum corneum at the end of application was studied in humans. For each anatomic site, 1,000 nmol of 14C-radiolabeled benzoic acid, benzoic acid sodium salt, caffeine, or acetylsalicylic acid was applied to 1-cm2 area of skin of male Caucasian patients aged 28 +/- 2 years (groups of 6-8). For each molecule and each site, a first application on the right-hand side of the body allowed total absorption to be determined by measuring the amount excreted in the urine. A second application, performed 48 h later on the contralateral site, enabled the total amount of substance present in the stratum corneum at the end of application (30 min) to be assessed after cellophane-tape stripping of the treated area. The results showed that skin permeability varied substantially, depending both on the physicochemical nature of the molecule and on the anatomical location. In general, the rank order in skin permeability of the studied areas appears to be as follows: arm less than or equal to abdomen less than postauricular less than forehead. Whatever the compound applied, the forehead was approximately 2 times as permeable as the arm or abdomen. Independent of the origin of the differences in permeability observed among sites, there exists a linear correlation (r = 0.97, p less than 0.001) between the amounts of substance present in the stratum corneum at the end of application (30 min) and the total amounts which penetrated within a 4-d period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

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

The 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.

Absorption↗
PubMed1987

The hairless rat: a relevant animal model to predict in vivo percutaneous absorption in humans?

Percutaneous absorption of 4 radiolabeled molecules was compared in the hairless rat (back) and in different anatomic sites in human (arm, abdomen, postauricular, forehead). The conditions under which these 4 compounds were administered (area treated, dose, vehicle, contact time, etc.) were similar in both species. The results showed that, in humans and rats, there exists the same rank order in total absorption: benzoic acid sodium salt less than caffeine less than benzoic acid less than acetylsalicylic acid. In both species there was a factor of 3 between the most and the least absorbed molecule. Although skin permeability varied significantly with the physicochemical nature of the compound administered, it also depended on the anatomic site involved. Independent of the molecule studied, the rank order of permeability of the sites tested in humans appeared as follows: arm less than or equal to abdomen less than postauricular less than forehead. There was a factor of 3 between the most and the least permeable sites. For each molecule and each anatomic site, the ratios of total percutaneous absorption human/hairless rat (back) were determined. For a given anatomic site and whatever the molecule tested, these ratios were constant. It thus appears that when conditions are carefully controlled, it may be possible, by measurements on animals, to predict the absorption of a compound in humans. Further experimentation with chemicals of varied physicochemical properties will be required for validation of the model.

Absorption↗
PubMed1986

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

The 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 less than arm less than chest less than thigh less than abdomen less than 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 less than 0.001).

Adult↗
PubMed1986

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.

Animals↗
PubMed1985

The measurement of the stratum corneum reservoir. A predictive method for in vivo percutaneous absorption studies: influence of application time.

The relation existing in vivo between the reservoir function of the stratum corneum following a 30-min application time and the total percutaneous absorption of molecules applied for a longer time was studied on hairless rats. One thousand nanomoles of 4 radiolabeled molecules (theophylline, nicotinic acid, acetyl salicylic acid, benzoic acid) were applied on 1 cm2 of back skin for 0.5, 2, 4, and 6 h. The total recovery in excreta and the whole animal body were measured 4 days later in order to determine the level of absorption. A direct proportionality (r = 0.99) between the total percutaneous absorption of these compounds and the duration of their application was observed. This suggests that a constant flux of penetration does exist in vivo. The reservoir function of the stratum corneum was measured by successive stripping of the treated area. Following a 30-min application, a strict correlation (r = 0.99) between the total amounts of molecules penetrated in 4 days and the amounts found in the reservoir of the horny layer was demonstrated. All together these findings show that the simple knowledge of the reservoir effect of the stratum corneum for a molecule applied for 30 min allows the predictive assessment of its total penetration resulting from various times of application.

Animals↗
PubMed1984

In vivo relationship between horny layer reservoir effect and percutaneous absorption in human and rat.

The in vivo relationship between the reservoir effect of the stratum corneum and the percutaneous absorption was established in both human volunteers and hairless rats. Four doses of [ring-14C]benzoic acid, 125, 250, 500, and 1000 nmol, were applied on 1 cm2 either on the external side of the human arm or on the back of the rat, for 30 min. In both human and rat, the data on percutaneous absorption after 4 days is directly related to the dose administered. In rat, the permeability to benzoic acid is twice that of the human skin and the reservoir effect of the stratum corneum, measured at the end of application (30 min), is also doubled for this molecule in rat. Taking into account these findings and the observed histologic differences between the treated areas of these two species, the molecular reservoir of the horny layer may well be situated within the interlayer spaces. For both species, a linear relationship exists between (x), the amount of substance present in the stratum corneum at the end of application (30 min), and (y), the total amount penetrated in 4 days. The relationship, similar to that obtained in an earlier study on rat with 10 molecules, may be written as follows: y = 1.83 x - 0.52 (r = 0.998, p less than 0.001). Thus the amount of substance liable to penetrate through human skin within 4 days can be predicted by measuring the amount present in the stratum corneum 30 min after application of the drug.

Administration, Topical↗
PubMed1983

In vivo correlation between stratum corneum reservoir function and percutaneous absorption.

A relationship between stratum corneum reservoir function and percutaneous absorption has been established in the hairless rat. Two hundred nanomoles of 10 substances that have a wide range of chemical structures were topically applied for 30 min and the total body distribution was measured after 96 h. The quantity of substance present in the stratum corneum reservoir after 30-min application was measured by liquid scintillation counting after tape-stripping the treated area. A linear relationship exists between the quantity of substance in this reservoir x(nmol X cm-2) and the total amount of radioactivity distributed in the body and excreta y(nmol X cm-2) after 96 h. The relationship is given by: y = 1.644 X x - 0.536 (r = 0.998, p less than 0.001). Apart from the steroids, 80-95% of the compounds were excreted in the urine; and with the exception of thiourea, this elimination was rapid, especially for mannitol and benzoic acid. We confirmed that in terms of penetration there is a factor of 50 between benzoic acid (best) and dexamethasone (worst). Thus the quantity of substance penetrating through intact rat skin can be predicted by measuring the horny layer concentration. The animal data reported here should be verified in humans.

Animals↗