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Biomedical subjects

R C Wester

Publications and source records attributed to R C Wester.

At least 73 records · Page 4Linked to original sources
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

Benzene levels in ambient air and breath of smokers and nonsmokers in urban and pristine environments.

Benzene levels in human breath and in ambient air were compared in the urban area of San Francisco (SF) and in a more remote coastal pristine setting of Stinson Beach, Calif. (SB). Benzene analysis was done by gas chromatography-mass spectroscopy (GC-MS). Ambient benzene levels were sevenfold higher in SF (2.6 +/- 1.3 ppb, n = 25) than SB (0.38 +/- 0.39 ppb, n = 21). In SF, benzene in smokers' breath (6.8 +/- 3.0 ppb) was greater than in nonsmokers' breath (2.5 +/- 0.8 ppb) and smokers' ambient air (3.3 +/- 0.8 ppb). In SB the same pattern was observed: benzene in smokers' breath was higher than in nonsmokers' breath and ambient air. Benzene in SF nonsmokers' breath was greater than in SB nonsmokers' breath. Marijuana-only smokers had benzene breath levels between those of smokers and nonsmokers. There was little correlation between benzene in breath and number of cigarettes smoked, or with other benzene exposures such as diet. Of special interest was the finding that benzene in breath of SF nonsmokers (2.5 +/- 0.8 ppb) was greater than that in nonsmokers ambient air (1.4 +/- 0.1 ppb). The same was true in SB, where benzene in nonsmokers breath was greater than ambient air (1.8 +/- 0.2 ppb versus 1.0 +/- 0.1 ppb on d 1 and 1.3 +/- 0.3 ppb versus 0.23 +/- 0.18 ppb on d 2). This suggests an additional source of benzene other than outdoor ambient air.

Adolescent↗
PubMed1985

Comparison of percutaneous absorption of fragrances by humans and monkeys.

The percutaneous absorption of two cosmetic fragrance materials, safrole and cinnamyl anthranilate, as well as of cinnamic alcohol and cinnamic acid, has been measured at occluded and non-occluded application sites. Absorption values were determined in the rhesus monkey in vivo. Absorption through human skin was measured by using excised skin in diffusion cells. Because of the insolubility in water of safrole and cinnamyl anthranilate, a nonionic surfactant solution (6% oleth 20) was used in the receptor chamber of the diffusion cell in order to facilitate the partitioning of the compounds from the skin into the receptor fluid. The relative volatility of the compounds was determined in order to aid in the interpretation of the absorption results. The greatest difference between in vivo and in vitro absorption values occurred with safrole, which was the least well absorbed and the most volatile compound. Cinnamic acid absorption through non-occluded human skin (17.8 +/- 4.9%, mean +/- SEM) was significantly lower than through monkey skin (38.6 +/- 8.3%). The values for absorption through human and monkey skin did not differ significantly for cinnamyl anthranilate (24.0 +/- 5.1% v. 26.1 +/- 2.3%) or cinnamic alcohol (33.9 +/- 7.3% v. 25.4 +/- 4.4%). Occlusion of the skin resulted in greater permeation of all of the compounds; a significant difference in permeability between the two types of skin occurred only with safrole. The fragrances were absorbed well, but their volatility must be considered in a toxicity evaluation. There was reasonable agreement between the values obtained from the studies of the human skin in vitro and the monkey skin in vivo.

Animals↗
PubMed1985

In vivo percutaneous absorption and decontamination of pesticides in humans.

Regulators today face complex problems in assessing the health hazards associated with the use of pesticides. Pesticide exposure occurs at manufacturing, application, work area, and consumption situations, and in the air, water, and soil of our daily lives. The skin is the largest organ of the body and thus has become a major environmental port for pesticides to enter the body. In this paper, we review the principles of percutaneous absorption--the rate and extent that chemicals enter the body through the skin--using data currently available for pesticides.

Animals↗
PubMed1984

In vivo percutaneous absorption of paraquat from hand, leg, and forearm of humans.

This study determines the in vivo percutaneous absorption of paraquat in humans. Three skin sites of application were used in a crossover manner for six subjects. The percents of applied dose (9 micrograms/cm2) absorbed were 0.29 +/- 0.2 (SD) for the leg, 0.23 +/- 0.1 for the hand, and 0.29 +/- 0.1 for the forearm. This gives an in vivo absorption rate of 0.03 microgram/cm2 for the 24-h exposure. Paraquat can be absorbed in vivo through the skin of humans; however, it is considered a minimally absorbed chemical.

Forearm↗
PubMed1984

Minoxidil stimulates cutaneous blood flow in human balding scalps: pharmacodynamics measured by laser Doppler velocimetry and photopulse plethysmography.

In a double-blind study with randomly assigned topical solutions of 0%, 1%, 3%, or 5% minoxidil, the blood flow in balding scalps of 16 human volunteers was measured by the noninvasive techniques of both laser Doppler velocimetry (LDV) and photopulse plethysmography (PPG). On two consecutive days, an 0.25-ml volume of the assigned minoxidil formulation was spread uniformly over a 100-cm2 area of each side of the bald scalp and cutaneous blood flow was recorded for the following 4 h. Both measurement techniques showed that the 5% minoxidil solution stimulated the microcirculation of the bald scalp. Increased blood flow was greater with the 5% minoxidil solution than with the other treatments. Measured by LDV on day 1, the increase (p less than 0.0001) in blood flow occurred within 15 min of application of the 5% solution of minoxidil and was maintained at least through hour 1. On day 2, LDV showed blood flow stimulation with the 5% solution was 3-fold (p less than 0.0001) within 15 min of application and was so maintained for about 1 h. Measured by PPG, the only statistically significant (p less than 0.01) response occurred with the day 2 application of the 5% minoxidil solution. PPG is dependent on local blood volume and is only weakly correlated to cutaneous blood flow, which makes it unsuitable for this kind of study. Analysis of vital signs for days 1 and 2 revealed no systemic effect from treatment with minoxidil, suggesting that the blood flow stimulation was directly related to the topical application of minoxidil.

Administration, Topical↗
PubMed1983

Malathion percutaneous absorption after repeated administration to man.

Prediction of exposure and toxic potential of pesticides such as malathion are routinely based upon acute exposure and single-dose percutaneous absorption determination. What has become obvious with pesticide exposure such as the malathion spraying for the medfly is that chronic daily exposure is the more relevant situation. Our objective was to determine the percutaneous absorption of chronically applied malathion in man and to compare chronic absorption to single-dose absorption. The experimental design was to first topically apply [14C]malathion to human male volunteers. This procedure was followed by repeated administration of nonradioactive malathion to the same site of application (ventral forearm). [14C]Malathion was reapplied (Day 8) when urinary excretion of radioactivity from the first application reached minimum detectable levels. The first [14C]malathion absorption was compared to the second [14C]malathion application. The percutaneous absorption from the first [14C]malathion application was 4.48 +/- 1.3% (SD) of the applied dose. The absorption from the second [14C]malathion administration was 3.53 +/- 1.0%, a value not significantly (p greater than 0.05) different from the first application. Therefore, for malathion the single-dose application data are relevant for predicting the toxic potential for longer-term exposure.

Administration, Topical↗
PubMed1983

Pharmacokinetics and bioavailability of intravenous and topical nitroglycerin in the rhesus monkey: estimate of percutaneous first-pass metabolism.

[14C]Nitroglycerin was administered intravenously and topically to three rhesus monkeys and the pharmacokinetics were determined. The rhesus monkey is an animal model for which percutaneous absorption is similar to that in the human. After intravenous administration the decline in plasma nitroglycerin concentration was biexponential with an initial half-life of 0.8 min (2-5 min postadministration) and a terminal half-life of 18 min (5-60 min postadministration). After topical application in an ointment, plasma concentrations of unchanged nitroglycerin were first detectable at 0.25 hr postapplication. Peak plasma nitroglycerin concentrations occurred between 4-6 hr, and nitroglycerin was still detectable at 24 hr postapplication. Plasma levels fit a biexponential curve with an alpha-phase half-life of 3.0 hr, a beta-phase half-life of 4.3 hr, and a lag time of 0.5 hr. The absolute bioavailability of topical nitroglycerin was 56.6 +/- 5.8%. The differences in bioavailability estimates between unchanged nitroglycerin and total carbon-14 is considered to be the amount of nitroglycerin which is metabolized as it is absorbed through the skin (percutaneous first-pass effect). This value for topical nitroglycerin was quite small, only 16-21% depending on the method of comparison.

Animals↗
PubMed1983

Noninvasive assessments of the percutaneous absorption of methyl nicotinate in humans.

Percutaneous penetration of the vasodilator methyl nicotinate (methyl 3-pyridinecarboxylate) has been monitored in vivo in humans with the noninvasive techniques of laser Doppler velocimetry and photopulse plethysmography. These optical methods use different technologies to generate a voltage output which is related to perfusion of the cutaneous microcirculation. The procedures are therefore sensitive to the pharmacologic stimulus and duration of local vasodilation. Following topical application of methyl nicotinate, excellent correlation was found between the response of both methods and the visual observation of erythema. Lower drug concentrations delayed the onset and magnitude of the response and shortened the time period for which elevated microperfusion was observed. These techniques appear to provide a useful noninvasive assessment of the time course of drug behavior in the region of skin to which topical application is made.

Erythema↗
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

In vivo percutaneous absorption of hydrocortisone in psoriatic patients and normal volunteers.

Our objective was to determine the percutaneous absorption of hydrocortisone in psoriatic skin. [14C]-Hydrocortisone formulated as a 0.5% cream was applied to sharply defined erythematous plaques with silvery scales on the dorsal forearm of four hospitalized psoriatic patients. An average 2.32 +/- 1.4 (SD) percent of the applied dose was absorbed. The absorption of the same dose from the dorsal forearm of six normal subjects was 2.45 +/- 1.2%. We conclude that for presumably stable psoriatic plaques, the percutaneous absorption of hydrocortisone is the same as for normal skin.

Adult↗
PubMed1980

Variations in percutaneous absorption of testosterone in the rhesus monkey due to anatomic site of application and frequency of application.

This study determines if the anatomic region affected percutaneous absorption in the rhesus monkey, an animal model with some relevance to man. Percutaneous absorption of testosterone (13.3 microgram/cm2) from the ventral forearm was 8.8 +/- 2.5%. Absorption from the chest was slightly less (5.3 +/- 0.6%) while that from the cheek was about the same (9.6 +/- 0.2%). Absorption from the scalp was greatly increased (20.4 +/- 2.7%), that from the vagina was the greatest (63.1 +/- 2.6%). As previously noted in man, anatomic variation in skin absorption exists in the rhesus. The ratio of scalp absorption to ventral forearm absorption in the rhesus was similar to that in man. The next objective was to determine the percutaneous absorption of testosterone when applied as a single dose or on a repetitive basis. There was no substantial difference in total absorption when 13.3 microgram/cm2 was applied as a single dose or when the 13.3 microgram/cm2 was applied three times, totaling 40 microgram/cm2. However, when 40 microgram/cm2 was applied as a single dose, absorption was substantially increased over 13.3 microgram/cm2 applied either once or three times. These results confirm previously reported results done with single versus repetitive doses of hydrocortisone.

Animals↗
PubMed1980

Percutaneous absorption of hydrocortisone increases with long-term administration. In vivo studies in the rhesus monkey.

This study compares percutaneous absorption of hydrocortisone after short and long-term administration. The experimental design was to first apply 14C-hydrocortisone. This was followed by long-term administration of nonradioactive hydrocortisone. Then 14C-hydrocortisone was applied again when urinary excretion of radioactivity from the first application reached minimum detectable levels. Short- (first 14C-hydrocortisone application) and long-term (second 14C-hydrocortisone application) penetrations were compared. The level of absorption of hydrocortisone significantly increased during long-term administration, whether applied in an acetone vehicle or in a 0.9% emulsion ointment base (Eucerin). A placebo study in which only an acetone vehicle was applied for a long period followed by 14C-hydrocortisone application showed no enhanced penetration. It is suggested that long-term application of hydrocortisone alters the penetration barrier, resulting in enhanced penetration. The relevance of this long-term corticosteroid use in man is possibly of great importance.

Acetone↗
PubMed1978

Topical bioavailability of a potential anti-acne agent (SC-23110) as determined by cumulative excretion and areas under plasma concentration time curves.

The topical bioavailability of a potential anti-acne agent ([14C]-SC-23110) was determined in the rhesus monkey, an animal model relevant to man. By the method of cumulative excretion in urine and feces the percutaneous absorption of 21 microgram/cm2 of the free base form was determined to be 0.58 +/- 0.16 (SD) percent of the applied dose. The mean areas under the plasma concentration time curves (AUC) following topical and intravenous administration were also determined. The ratior of the AUC's following topical and iv administration gave a bioavailability of 0.49% of the applied dose, a value in good agreement with the 0.58% obtained by cumulative excretion. Plasma AUC curves can be used to determined the percutaneous absorption (bioavailability) of compounds. Percutaneous absorption of [14C]-SC-23110 (80 microgram/cm2) when topically applied as the salt or free base form was compared. Twice the amount of compound was absorbed as the free base (0.34%) than as the salt (0.17%).

Acne Vulgaris↗