Drug Targeting Efficacy to Underlying Muscle Following Topical Application. I. Evaluation Based on a Physiological Pharmacokinetic Model.

Abstract

A physiological pharmacokinetic model describing the absorption and disposition of topically applied drugs was proposed, and the effect of various pharmacokinetic and physiological parameters on the drug delivery into the targeted muscle was simulated. The proposed model consists of vehicle, and stratum corneum, viable epidermis and muscle below the application and reference sites, and plasma, each joined with transfer clearance and plasma flow. Indomethacin concentrations in tissues and plasma after topical application to rats could be explained by the model. Most indomethacin delivered into the underlying muscle was via direct penetration. The model simulation showed that the increase in plasma clearance and clearance between viable skin and muscle, and the decrease in application area and plasma flow rate into viable skin and muscle would promote the targeting efficacy of topically applied drugs to the underlying muscle.

In Silico Estimation of Skin Concentration of Dermally Metabolized Chemicals

“…One assumption is that the concentrations of both parent and metabolized chemicals in the plasma are negligible low compared with those in the dermis. In fact, indomethacin concentrations in the underlying tissues was 1000-10000 fold higher than those in the plasma following topical application [24].…”

“…Skin permeation parameters, which were required to predict the skin concentrations of the parent compound and its metabolite, were obtained by fi tting permeation data under various conditions to the diffusion models [22]. f ) were taken from the literatures [11,23,24]. Table 1 were determined from the permeation data after application EN to the skin treated with DFP, a serine protease inhibitor (Figures 2c and d).…”

Reawakening Atlas: Chemical Approaches To Repair or Replace Dysfunctional Musculature

“…From the prospect of enhancing skeletal muscle regeneration, the development of small molecule cocktails that induce skeletal muscle regeneration are undoubtedly exciting, but there is currently no strategy to directly apply these in animal models of muscle degeneration. Improvements in drug delivery systems and their targeting to specific tissues, such as skeletal muscle, − offers hope that these small molecule modulators of muscle regeneration can be further developed as promising therapeutics. From the perspective of small molecule approaches for treating cardiac disease, it can be seen that from the relatively large number of small molecule inducers of cardiogenesis, only five have been shown to be effective in animal models of heart disease (Figure ).…”