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Biomedical subjects

B Gabard

Publications and source records attributed to B Gabard.

34 records · Page 2Linked to original sources
PubMed1993

Ibuprofen epidermal levels after topical application in vitro: effect of formulation, application time, dose variation and occlusion.

The influence of vehicle (two oil-in-water emulsions and two gels, each containing 10% or 5% ibuprofen) application time (0.5, 1, 2 h), applied dose (1.5, 3, 6, 12 mg/cm2), time (24 h after an 0.5 h application time), and occlusion on the epidermal concentration of ibuprofen was investigated. The drug concentration in the epidermis was measured by HPLC. All results were expressed as microgram drug/mg epidermal protein. The application time had no influence on the epidermal drug concentration, whereas the two gel formulations produced concentrations approximately twice those obtained with the emulsions. A significant positive correlation was found between the applied dose and the epidermal concentration for each formulation. After 24 h the amount of drug remaining in the epidermis was low (reduced by factors of 10-20). Occlusion produced higher concentrations, but only with the 2-h application time. The methods are reliable, and useful in ranking vehicles according to their ability to release ibuprofen into the epidermis. Future investigations should explore the relationship between epidermal concentration and anti-inflammatory efficacy in vivo.

Administration, Topical↗
PubMed1993

Feasibility of measuring the bioavailability of topical ibuprofen in commercial formulations using drug content in epidermis and a methyl nicotinate skin inflammation assay.

A method has been developed which simultaneously compares the inhibition of an inflammation induced by a methyl nicotinate assay with the concentration of drug in the human epidermis determined in vitro following topical application of two 10% ibuprofen formulations. The bioavailability of drug from commercial gel and emulsion was assessed after the application of various doses (3, 6 and 12 mg/cm2) and an application time of 0.5 h at two time points: 0.5 and 24 h (only with the 12 mg/cm2 dose) after the removal of the non-steroidal anti-inflammatory drug (NSAID) from the skin. In parallel, we assessed the epidermal concentration of the drug in vitro and evaluated the anti-inflammatory effect of the topicals in vivo. A correlation (r = 0.9603, p < 0.001) between the amount of drug in the epidermis expressed as micrograms per milligram of epidermal protein and the corresponding inhibition of the inflammation was observed. Increasing the amount of drug in the epidermis correlated with an increased inhibition of the inflammation. The gel formulation released more drug to the skin and produced a greater anti-inflammatory effect. Topical NSAID concentration in treated skin can therefore be determined and correlates well with the resulting pharmacodynamic activity. This approach will likely have utility in optimizing topical NSAIDs.

Administration, Topical↗
PubMed1991

Endogenous plasma N-acetylcysteine and single dose oral bioavailability from two different formulations as determined by a new analytical method.

A method to quantitate N-acetylcysteine in plasma using reductive cleavage with tributylphosphine and post-HPLC column derivatisation with omicron-phthalaldehyde is described. Using this method, endogenous average concentrations of 0.08 microM were measured in 10 volunteers participating in a crossover study to compare the bioavailability of two different formulations of N-acetylcysteine. The drug was detected in plasma for up to 12 h after administration of a single oral dose (200 mg); the Cmax values were up to 20 times the endogenous levels. The sensitivity and selectivity of the method should thus enable the behaviour of N-acetylcysteine after oral administration to be properly described and bioavailability studies to be performed.

Acetylcysteine↗
PubMed1989

[Salicylic acid and urea--possible modification of the keratolytic effect of salicylic acid by urea].

The keratolytic effect of salicylic acid was measured with a colorimeter after staining the outer layers of the stratum corneum with silver nitrate. Salicylic acid was used in a concentration of 5% or 10% in vaseline or of 5% in an improved vehicle. The results of two experiments showed that improvement of the vehicle increased the keratolytic effect of salicylic acid and that urea played a major role in this improvement.

Dermatologic Agents↗
PubMed1986

Effect of an extract of Ginkgo biloba on triethyltin-induced cerebral edema.

The effect of an extract of Ginkgo biloba was studied on cerebral edema in rats intoxicated with triethyltin chloride (TET). Brains of TET-treated rats showed elevated water and sodium levels and a significant increase in the sodium/potassium ratio. Animals treated with TET plus the extract did not show water and electrolyte changes. The course of intoxication and treatment was studied light- and electron-microscopically. A severe edema with extensive vacuolization was seen in the cerebral and cerebellar white matter. Morphometric measurements revealed a significant decrease in these manifestations of the cytotoxic edema when the animals were treated with an extract of Ginkgo biloba. Thus, we conclude that this extract has a protective effect on the development of a cytotoxic edema in the white matter of the brain.

Animals↗
PubMed1980

Removal of internally deposited gold by 2,3-dimercaptopropane sodium sulphonate (Dimaval).

1 Orally administered 2,3-dimercaptopropane sodium sulphonate (DMPS, Dimaval) reduced the concentration of gold in rats treated with Auro-Detoxin and increased the urinary excretion of the metal. 2 In a long-term experiment, DMPS decreased significantly the concentration of gold in the kidneys and in the skin and increased it in plasma. 3 DMPS appears to be of interest as a possible antidote to gold, which could replace the more toxic 2,3-dimercaptopropanol (BAL).

Animals↗
PubMed1980

Toxicological studies on sodium 2,3-dimercaptopropane-1-sulfonate in the rat.

The toxicity of Na-2,3-dimercaptopropane-1-sulfonate (DMPS) was investigated in rats. The lethality after large i.p. doses is diminished by a factor of approx. 6 if a single dose is divided into several doses on consecutive days. Chronic treatment with 600 mumol DMPS/kg and day p.o. did bring about adverse effects except a reduction in Cu-concentration in some organs, especially in the kidneys, immediately after DMPS-treatment, which was normalized within 1 week. The offspring of DMPS treated female rats showed no abnormalities.

Animals↗
PubMed1979

Note on the metabolism of the mercury chelating agent sodium 2,3-dimercaptopropane-1-sulfonate.

Chromatographic analysis of the radioactive urine obtained after injection into rats of [1,3-(14)C] dimercaptopropane sodium sulfonate (DMPS, Dimaval) showed that part of the administered chelating agent is excreted unchanged. This was confirmed by the results of studies of sulfur excretion in the different fractions of the urine as well as by titration of the excreted thiol groups. The results show that, at least in rats, DMPS is not involved in important metabolic reactions.

Animals↗
PubMed1978

Distribution and excretion of the mercury chelating agent sodium 2,3-dimercaptopropane-1-sulfonate in the rat.

The distribution and excretion of sodium 2,3-dimercapto-1,3 14C-propane-1-sulfonate as dependent on time has been studied in the rat. The highest concentration is found in the kidneys, the lowest in the brain. The excretion is very rapid (T1/2 = 19 min) and follows a monoexponential curve during the first hour after administration. This holds for plasma and most of the organs too. The apparent distribution volume of the radioactivity is equivalent to the volume of the extracellular water. After oral administration, 30-40% is absorbed from the gut. The results lead to the conclusion that a fraction of the drug is weakly bound to plasma- and membrane-proteins. They are discussed with respect to the treatment of heavy metal poisoning.

Animals↗
PubMed1976

The excretion and distribution of inorganic mercury in the rat as influenced by several chelating agents.

Among 15 chelating agents tested, sodium-2,3-dimercaptopropane 1 sulfonate (DMPS), 2,3-dimercaptopropanol (BAL), sodium-mercaptoethyliminodiacetate (MEIDA), and D-penicillamine (PA) exerted an influence on the excretion of Hg and its distribution in the organs. The excretion pattern however, is different for these compounds, and, from the practical point of view, a favourable effect is exhibited only by DMPS which enhances the urinary excretion rate and lowers the Hg-concentration in all organs.

Animals↗
PubMedDate not supplied

A qualitative estimate of the influence of halcinonide concentration and urea on the reservoir formation in the stratum corneum.

The existence of a stratum corneum reservoir for topically applied substances is well known. Data concerning the stratum corneum retention time are important for the elaboration of optimal topical treatment. We used the re-occlusion technique followed by skin colour measurements (Chromametry) for the evaluation of the stratum corneum retention time of halcinonide. We found a significant reservoir for halcinonide up to 5 days after the initial application. The retention was found to be corticosteroid concentration and formulation dependent.

Administration, Topical↗
PubMedDate not supplied

Skin penetration and sun protection factor of five UV filters: effect of the vehicle.

To gain information about efficacy and safety of sunscreens, we compared the skin penetration of ultraviolet (UV) filters from two vehicles, i.e. an oil-in-water (O/W) emulsion gel and petrolatum jelly both in vitro and in vivo, as well as the corresponding pharmacological effect, i.e. the sun protection factor (SPF) in vivo. The UV filters studied were benzophenone-3 (BPH), ethylhexyl methoxycinnamate (EHM), butyl methoxydibenzoyl methane, ethylhexyl salicylate and homosalate. The human skin penetration of these five chemicals from the two vehicles was determined both in vitro using Franz cells and in vivo using a standardized tape-stripping method. The SPF of the two sunscreens was determined in vivo following the COLIPA guidelines. In vitro none of the filters permeated through the skin after 6 h of product application and very little could be found in the skin. BPH and EHM were the only UV filters found in the dermis (both after 30 min and 6 h). An effect of the vehicle could be noticed only for BPH after 30 min in the dermis and 6 h in both dermis and epidermis. In vivo, no differences in the amount of individual UV filters (in % of the applied dose) in the 15 first strips of the stratum corneum (SC) were found following 30 min of application of the formulations; however, the amount of UV filters that were retained in the SC was significantly higher (around 3 times) with the O/W emulsion gel than with the petrolatum jelly. This difference between the two vehicles was also of consequence for the SPF in vivo measured 30 min after application of the products (SPF congruent with 18 with the O/W emulsion gel compared to SPF congruent with 10 with the petrolatum jelly). By choosing the right vehicle or optimizing it, not only sunscreen products can be significantly improved in terms of pharmacological efficacy but the potential toxicological risk associated with the skin penetration of UV filters may be significantly reduced.

Adult↗