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At least 109 records · Page 6Linked to original sources
PubMed1991

Methods for in vitro skin absorption studies of a lipophilic toxin produced by red tide.

The penetration and distribution of [3H]PbTx-3 into pig skin was determined using in vivo and in vitro methods. The dose used in each topical study was 0.3-0.4 micrograms/cm2 skin, with dimethylsulfoxide as the vehicle. In the in vivo study, mean cutaneous absorption after 48 h (expressed as percentage of the dose) was 11.5% (n = 3). In the in vitro study, mean cutaneous absorption after 48 h was 1.6% (n = 12), when based on accumulation of radioactivity in receptor fluid, or 9.9% when based on receptor fluid and dermis. [3H]PbTx-3 readily penetrated through the epidermis into the dermis, reaching maximal dermal accumulation at 4 h (9.1% in vivo and 18% in vitro). At 24 h, the amount in the dermis decreased to 2.3% and 15% in vivo and in vitro, respectively and at 48 h the amount in the dermis decreased to 8.2% in vitro. These results demonstrate the important role of the dermis as a reservoir for a lipophilic compound in both in vivo and in vitro percutaneous absorption studies.

Administration, Topical↗
PubMedDate not supplied

[Iontophoresis of forced skin absorption of indomethacin and salicylic acid].

Cutaneous absorption of ionized substances is forced by iontophoresis. This was shown by Pratzel and Hillmeier's investigation of the permeation of salicylic acid (increasing factor 150) and Pratzel and Dittrich's experiments with indomethacin (factor 10) in pigs. In the present paper it is shown that in human volunteers iontophoretic application of indomethacin for one hour onto the skin of the back (surface 1380 cm2) increased indomethacin plasma levels after 2 hours to a maximum of 221 ng/ml, and increased urinary excretion of indomethacin from 24 micrograms (control) to 138.7 micrograms in 5 hours. Iontophoretic application of salicylic acid for one hour daily in human volunteers onto a skin area of 400 cm2 increased serum levels in five days to 690 ng/ml and urinary excretion of salicylic acid and salicyluric acid to 24 mg, as opposed to 2.5 mg by control without current. However, after 30 min iontophoresis only 4 mg is excreted in the urine. In conclusion, if the iontophoresis is practised over a long period of time on large skin areas, systemic effects can be expected.

Administration, Topical↗
PubMed2000

Pharmacokinetics, skin absorption, stability, blood partition, and protein binding of AS 2-006A, a new wound healing agent.

After intravenous administration of AS 2-006A, 20, 50, and 90 mg/kg, to rats, the pharmacokinetic parameters, terminal half-life (69.8-86. 6 min), mean residence time (56.2-75.2 min), apparent volume of distribution at steady state (809-1040 mL/kg), and total body clearance (11.4-11.9 mL/min/kg), were dose-independent. After topical application of 0.5 or 1% AS 2-006A ointment, 300 mg, to abraded rat skin, the absorbed amounts were dose (0.5 and 1%) and time (30, 60, 120, 240, 360 and 480 min)-independent; the value was approximately 20%. The tissue-to-plasma ratios of AS 2-006A were greater than unity in all rat tissues studied, except in the muscle and large intestine. AS 2-006A was stable for up to 24 h incubation in rat plasma, and human plasma and urine; however, it seemed not to be stable in rat urine; the disappearance rate constant was 0.0218/h. AS 2-006A reached equilibrium fast between plasma and blood cells, and the equilibrium plasma/blood cells partition ratios were independent of the initial rabbit blood concentrations of AS 2-006A, 10, 20, and 50 microg/mL; the mean values were in the range of 2.38-2.75 for three rabbit blood. The protein binding of AS 2-006A to rat plasma was high, as the drug was under detection limit in the filtrate at the plasma concentrations of the drug, ranging from 7.21 to 228 microg/mL.

Animals↗
PubMed1978

Pulmonary edema following skin absorption of organophosphate insecticide.

We report a case of acute pulmonary edema following exposure to organophosphate insectocide. Hypoxia, respiratory failure, and parasympathetic discharge are implicated in the pathogenesis and are related to the anticholinesterase activity of the toxicant. Rapid onset of acute pulmonary edema without cardiomegaly followed by prompt clearing are the radiographic features.

Child↗
PubMed1995

Pulmonary damage due to paraquat poisoning through skin absorption.

A case of recovery from acute respiratory insufficiency due to paraquat is described. A 57-year-old farmer developed breathlessness, high fever and interstitial infiltrates in the upper and middle lung fields few days after percutaneous paraquat poisoning with rapid evolution to pulmonary fibrosis. Anti-inflammatory drugs and antioxidants, were administered to the patient, though with a delay, with some improvement; the patient survived despite residual lung fibrosis. Paraquat lung, as confirmed by this paper, is not invariably fatal.

Acute Disease↗
PubMed1989

[Skin absorption of volatile oils. Pharmacokinetics].

Volatile oils are frequently employed in the local treatment of pain. 1,8-Cineole, the principal component of eucalyptus oil, was used as a model substance to determine whether this active component can be detected in effective amounts at the target area in the skeletal muscles after dermal application. The investigation showed surprisingly large differences depending on the manner of application. The relative bioavailability of the model substance 1,8-cineole obtained by using an applicator was 320% as compared with that obtained by using an occlusive dressing. This has practical effects on the dosage and on the frequency of application.

Administration, Topical↗
PubMed1992

[Skin absorption promotors].

Transdermal penetration of drugs is currently much studied because it presents several attractive aspects, avoiding first past effects and offering means of immediate breaking of the therapeutic in case of hitch. But it must overcome the very efficient hindrance of the epidermal barrier. Few among the molecules have prerequisite structural and pharmacodynamical aspects necessary to this way of penetration. Substances belonging to diverse chemical families enhance sometimes largely this passage; they are named "penetration enhancers". In this review are listed the ideal properties of enhancers, the chemical structure of the currently more used ones, the possible interaction with other components of the formula in the case of TTS and towards the patient.

Administration, Cutaneous↗
PubMed1984

Skin absorption as a source of error in biological monitoring.

Concentrations of toluene, tetrachloroethylene, and 1,1,1-trichloroethane were determined in blood collected from both forearms of subjects after one of their hands was soaked for 5 min in the corresponding solvent or in a thinner containing toluene, as a simulation of the washing of hands with solvent after work. The concentrations of toluene, tetrachloroethylene, and 1,1,1-trichloroethane on the soaked side were high, maximally 5.4, 9.0, and 4.0 mumol/l, respectively, and 20-, 130-, and 35-fold, respectively, compared to the contralateral side. Intraindividual differences were very marked, and dramatic changes were detected within a short period of time. It was not until after 3 h with toluene and 5 h with the chlorinated solvents that the difference between the two arms vanished. It is concluded that analyses of solvents in blood specimens drawn during or immediately after the workday may lead to markedly erroneous estimations of exposure.

Environmental Exposure↗
PubMed2002

Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions.

We have simulated diffuse reflectance spectra of skin by assuming a wavelength-independent scattering coefficient for the different skin tissues and using the known wavelength dependence of the absorption coefficient of oxy- and deoxyhaemoglobin and water. A stochastic Monte Carlo method is used to convert the wavelength-dependent absorption coefficient and wavelength-independent scattering coefficient into reflected intensity. The absorption properties of skin tissues in the visible and near-infrared spectral regions are estimated by taking into account the spatial distribution of blood vessels, water and melanin content within distinct anatomical layers. The geometrical peculiarities of skin histological structure, degree of blood oxygenation and the haematocrit index are also taken into account. We demonstrate that when the model is supplied with reasonable physical and structural parameters of skin, the results of the simulation agree reasonably well with the results of in vivo measurements of skin spectra.

Absorption↗
PubMedDate not supplied

Environmental contamination and assessment of exposure to antineoplastic agents by determination of cyclophosphamide in urine of exposed pharmacy technicians: is skin absorption an important exposure route?

In the Netherlands, special guidelines and safety precautions were introduced about 10 y ago for preparation and administration of antineoplastic agents. However, little is known about the effectiveness of these measures. In this study, occupational exposure to antineoplastic agents of nine pharmacy technicians who were involved in drug preparation was investigated. Cyclophosphamide, 5-fluorouracil, and methotrexate accounted for 95% of the antineoplastic agents prepared; therefore, the presence of these compounds was monitored. During preparation, cyclophosphamide was detected in the air of the work environment (< 0.04-10.1 micrograms/m3). Contamination of and permeation through latex gloves were found for each of the three compounds. The uptake of cyclophosphamide was assessed by the determination of cyclophosphamide in urine. The drug was found in urine samples of six pharmacy technicians, including three persons who were not directly involved in the preparation of cyclophosphamide. The amounts excreted ranged from 0.2 to 19.4 micrograms/24 h. The results strongly suggest that inhalation is of minor importance for internal exposure, compared with other, presumably dermal, routes.

Absorption↗
PubMed1990

Percutaneous absorption and skin decontamination of PCBs: in vitro studies with human skin and in vivo studies in the rhesus monkey.

Knowledge of the entry of polychlorinated biphenyls through the skin into the body and subsequent disposition aids estimation of potential for human health hazard. [14C]Aroclor 1242 and [14C]Aroclor 1254 were separately administered intravenously and topically to rhesus monkeys. Following iv administration, 30-d excretion was 39.4 +/- 5.9% urine and 16.1 +/- 0.8% feces (total 55.5 +/- 5.1%) for Aroclor 1242, and 7.0 +/- 2.2% urine and 19.7 +/- 5.8% feces (total 26.7 +/- 7.5%) for Aroclor 1254. Mineral oil and trichlorobenzene are common PCB cosolvents in transformers. Skin absorption of Aroclor 1242 was 20.4 +/- 8.5% formulated in mineral oil and 18.0 +/- 3.8% in trichlorobenzene (p greater than .05). Absorption of Aroclor 1254 was 20.8 +/- 8.3% in mineral oil and 14.6 +/- 3.6% in trichlorobenzene (p greater than .05). PCBs are thus absorbed through skin, and excretion from the body is slow. Vehicle (trichlorobenzene or mineral oil) did not affect percutaneous absorption. In vitro skin absorption in human cadaver skin did not correlate with in vivo findings. This was due to lack of PCB partition from skin into the water receptor fluid, even with addition of 6% Oleth 20 (Volpo 20) solubilizer. Skin decontamination of PCBs showed soap and water to be as effective as or better than the solvent ethanol, mineral oil, and trichlorobenzene in removing PCBs from skin. There is a dynamic time lapse for PCBs between initial skin contact and skin absorption (irreversible removal). Thus initially most PCBs could be removed from skin, but this ability decreased with time to the point where at 24 h only about 25% of the initial PCB skin dose could be recovered with skin washing.

Administration, Topical↗