Multi ‐phase Multi‐Layer Mechanistic Dermal Absorption (MPML MechDermA) Model to predict local and systemic exposure of drug products applied on skin

AbstractPhysiologically based pharmacokinetic (PBPK) models combine knowledge about physiology, drug product properties such as physicochemical parameters, absorption, distribution, metabolism, excretion (ADME) characteristics, formulation attributes, and trial design or dosing regimen to mechanistically simulate drug pharmacokinetics. The current work describes the development of a multi-phase, multi-layer mechanistic dermal absorption (MPML MechDermA) model within the Simcyp ® Simulator capable of simulating uptake and permeation of drugs through human skin following application of drug products to the skin. The model was designed to account for formulation characteristics as well as body site- and sex- population variability to predict local and systemic bioavailabili ty. The present report outlines the structure and assumptions of the MPML MechDermA model and includes results from simulations comparing absorption at multiple body sites for two compounds, caffeine and benzoic acid, formulated as solutions. Finally, a model of the Feldene® (piroxicam) topical gel , 0.5% was developed and assessed for its ability to predict both plasma and local skin concentrations when compared to in vivo pharmacokinetic (PK) data.
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Tags: ARTICLE Source Type: research