Multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA) model to predict local and systemic exposure of drug products applied on skin.
Multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA) model to predict local and systemic exposure of drug products applied on skin.
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DOI：
10.1002/psp4.12814
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发表时间：
2022-08
影响因子：
3.5
通讯作者：
Polak, Sebastian
中科院分区：
文献类型：
--
作者：
Patel, Nikunjkumar;Clarke, James F.;Salem, Farzaneh;Abdulla, Tariq;Martins, Frederico;Arora, Sumit;Tsakalozou, Eleftheria;Hodgkinson, Arran;Arjmandi-Tash, Omid;Cristea, Sinziana;Ghosh, Priyanka;Alam, Khondoker;Raney, Sam G.;Jamei, Masoud;Polak, Sebastian
基于生理学的药代动力学模型结合了有关生理学、药品特性（例如理化参数、吸收、分布、代谢、排泄特征、制剂属性以及试验设计或给药方案）的知识，以机械地模拟药物药代动力学（PK）。目前的工作描述了 Simcyp 模拟器中多相、多层机械真皮吸收 (MPML MechDermA) 模型的开发，该模型能够模拟将药品涂抹到皮肤后通过人体皮肤的吸收和渗透。该模型旨在考虑制剂特征以及身体部位和性别群体的变异性，以预测局部和全身的生物利用度。本报告概述了 MPML MechDermA 模型的结构和假设，并包括对配制为溶液的两种化合物（咖啡因和苯甲酸）在多个身体部位的吸收进行比较的模拟结果。最后，开发了 0.5% Feldene（吡罗昔康）局部凝胶模型，并与体内 PK 数据相比，评估了其预测血浆和局部皮肤浓度的能力。
Physiologically‐based pharmacokinetic models combine knowledge about physiology, drug product properties, such as physicochemical parameters, absorption, distribution, metabolism, excretion characteristics, formulation attributes, and trial design or dosing regimen to mechanistically simulate drug pharmacokinetics (PK). The current work describes the development of a multiphase, multilayer 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 bioavailability. 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 PK data.
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影响因子：
3.8
作者：
ELIAS, PM
通讯作者：
ELIAS, PM
影响因子：
3.5
作者：
Abduljalil, K;Edwards, D;Barnett, A;Rose, R H;Cain, T;Jamei, M
通讯作者：
Jamei, M
影响因子：
3.7
作者：
Chen, Longjian;Han, Lujia;Lian, Guoping
通讯作者：
Lian, Guoping
DOI：
10.1016/j.ejpb.2018.07.015
发表时间：
2018-09-01
影响因子：
4.9
作者：
Amarah, A. A.;Petlin, D. G.;Anissimov, Y. G.
通讯作者：
Anissimov, Y. G.
影响因子：
3.9
作者：
Abduljalil, Khaled;Cain, Theresa;Rostami-Hodjegan, Amin
通讯作者：
Rostami-Hodjegan, Amin