PERCUTANEOUS-ABSORPTION OF BETAHISTINE THROUGH RAT SKIN AND PHARMACOKINETIC ANALYSIS OF THE PLASMA-CONCENTRATION

The percutaneous absorption of betahistine (BH) through rat skin was i nvestigated by in vitro and in vivo studies. Additionally, to describe the plasma BH profile observed, a simple pharmacokinetic model, the t wo-compartment model including a zero-order absorption process, was pr esented. BH penetrated well from gel or adhesive formulations in the p resence of an absorption enhancer (laurocapram and lauric acid) throug h rat skin, except for the formulation containing a lipid disperse sys tem of BH, from which the in vitro penetration rate was the lowest of all formulations tested. In vivo, the drug was also absorbed through t he skin from the formulations with enhancer. The gel formulation conta ining the lipid disperse system gave the highest and sustained plasma levels of BH, in contrast to the in vitro data, suggesting that this s ystem would provide a drug delivery system capable of maintaining an e ffective plasma concentration for a prolonged time. The model successf ully described the plasma levels of BH resulting from the rapid absorp tion during the initial time stage and the subsequent sustained absorp tion.