Pharmacodynamic Measurements of Methyl Nicotinate Percutaneous Absorption

Abstract

The local kinetics of percutaneous absorption provide information of relevance to the treatment of skin diseases and to the potential efficacy of transdermally delivered chemotherapy for systemic effect. This paper describes two non-invasive procedures (laser Doppler velocimetry and photopulse plethysmography) which permit pharmacodynamic measurements of methyl nicotinate skin penetration to be made in vivo in man. The methods are sensitive to the local vasodilative action elicited by the nicotinic acid ester. Dose-response behavior as a function of time has been monitored (1) over the concentration range 5–100 mM, and (2) by variation of drug application time and administration area. At the higher concentrations used, the magnitude of the erythemal response is saturable, and the effect is then progressively prolonged by further increasing the applied dose. Analysis of the data permits assessment of (a) the kinetics of drug delivery to and depletion from the site of action, and (b) the hypothetical level of steady state drug input necessary to sustain 50 % of the maximum detected response. Measurements of the type described here may prove useful, therefore, for elucidating otherwise inaccessible aspects of transcutaneous kinetics in vivo.