An improved model for studies on transdermal drug absorption in-vivo in rats.

Abstract

In rats, transdermal drug absorption can be studied under physiological conditions by cannulating the peripheral skin vein, draining the are of the skin which is used for drug application, and collecting the blood. This method leads to decreased blood volume, which causes a reduction in skin blood flow and limits the maximal duration of the experiment. We improved the model by replacing the collected blood with blood from donor animals, so enabling the measurement of transdermal absorption over a period of 5 h under near constant conditions of blood pressure, haematocrit and skin blood flow. The model was applied to the transdermal absorption of [3H]prazosin and [3H]scopolamine and their permeability coefficients, fluxes and lag-times were determined. The model is suitable for measurements of transdermal drug absorption under in-vivo conditions, both for comparison of absorption profiles of different drugs and of the same drug in different formulations.