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Biomedical subjects

R H Guy

Publications and source records attributed to R H Guy.

154 records · Page 9Linked to original sources

Physicochemical interpretation of the pharmacokinetics of percutaneous absorption.

Theoretical expressions are derived to predict the amount of a drug reaching the dermal capillaries as a function of simple physicochemical parameters. The mathematical approach involves the solution of the diffusion equation for the drug in the skin using the technique of Laplace transformation. First-order kinetics are assumed for the absorption of drug from the vehicle into the skin and for uptake into the capillaries. The relative importance of these different processes (absorption from vehicle, diffusion through the skin, and capillary removal) involved in the percutaneous penetration of a drug is discussed, and their influence upon the time course of the absorption phenomenon is illustrated.

Chemical Phenomena↗

Basal perfusion of the cutaneous microcirculation: measurements as a function of anatomic position.

Noninvasive optical techniques of photopulse plethysmography (PPG) and laser Doppler velocimetry (LDV) have been used to identify regional variations in the basal skin blood flow of humans. The procedures assess either the volume (PPG) or the volume-velocity product (LDV) of cutaneous blood vessel perfusion. Fifty-two anatomic positions have been studied in 10 normal subjects resting horizontally. The mean perfusion levels were ranked to reveal the variations in cutaneous blood flow as a function of body site. Groups of data were collected into cohorts and average perfusion values for the subjects within each cohort were compared by the Newman-Keuls multiple comparison test. Most transparently, the results reveal a collection of regions (fingers, palms, face, ears) for which cutaneous perfusion is much higher than all other positions. More subtle differences and some unexpected similarities, however, are also apparent and, in some cases, agree or, in others, conflict, with previously published information. With some exceptions, good general agreement between the two techniques was observed.

Adult↗

Noninvasive assessment of local nicotinate pharmacodynamics by photoplethysmography.

The local pharmacodynamics of a topical vasodilator (methyl nicotinate) has been followed noninvasively using photopulse plethysmography. This technique is sensitive to changes in blood flow through the cutaneous microcirculation and responds to the pharmacologic stimulus of the vasoactive agent employed. Five different application sites for the drug were studied and the time course of the local effect (i.e., onset, duration, and decay) was recorded. The applied amount of drug elicited, within a short period, a response which was saturable such that the observed increase in blood flow reached a plateau level. The decay of the elevated perfusion required approximately 1 h, suggesting a half-life for elimination of the drug from the skin of about 10 min. This result agrees closely with other reported values and suggests that the pharmacodynamic measurements of this study may prove useful in elucidating aspects of dermal pharmacokinetics.

Administration, Topical↗

Rapid radial transport of methyl nicotinate in the dermis.

Topical application of a sufficiently concentrated aqueous solution of methyl nicotinate elicits within minutes an erythematous, vasodilatory response in humans. In this study the radial increase of the erythematous area visible in the skin has been followed as a function of solution application time and methyl nicotinate concentration. Because of the nature of the physiological response, the observations are interpreted in terms of the dermal movement of the drug. The rate of radial spread was much more rapid than can be accounted for in terms of simple diffusion, and a mechanism involving transport by the blood flowing in the dermal vasculature is proposed.

Biological Transport↗

Diffusion of lysozyme chloride in water and aqueous potassium chloride solutions.

The diffusion of lysozyme chloride in aqueous solution has been studied at 25 degrees C using the Goüy interferometric technique. The concentration dependence of the diffusion coefficient in water has been measured over the concentration range 1.1599-9.1556 gcm-3 and the results suggest a value of D 25, w at infinite dilution of 5.838 x 10(-6) cm2s-1. The variation in diffusion coefficient with ionic strength has also been considered by following the diffusion of 0.45% lysozyme chloride in a series of potassium chloride solutions. The value of D in 0.15 M KCl has been found to be approximately one quarter of that in water alone an the diffusion coefficient has been shown to increase markedly as the KCl concentration is reduced below 0.05 M. Interpretation of these observations involves consideration of solution electrostatic effects.

Chemical Phenomena↗