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丙二醇经皮渗透:体外测量人腹部皮肤的吸收并与 QSAR 模型比较。

Dermal penetration of propylene glycols: measured absorption across human abdominal skin in vitro and comparison with a QSAR model.

机构信息

E.I. Du Pont de Nemours and Company, DuPont Haskell Global Centers for Health & Environmental Sciences, Newark, DE, USA.

出版信息

Toxicol In Vitro. 2011 Dec;25(8):1664-70. doi: 10.1016/j.tiv.2011.07.003. Epub 2011 Jul 18.

Abstract

The dermal penetration of undiluted monopropylene glycol (MPG) and dipropylene glycol (DPG) has been measured in vitro using human abdominal skin under conditions of infinite dose application, and the results compared with predictions from the SKINPERM QSAR model (ten Berge, 2009). The measured steady-state penetration rates (Jss) for MPG and DPG were 97.6 and 39.3 μg/cm2/h, respectively, and the permeability coefficients (Kp) were 9.48×10(-5) cm/h for MPG and 3.85×10(-5) cm/h for DPG. In comparison, the SKINPERM model slightly over-predicted Jss and Kp for MPG and DPG by between 2.6- and 5.1-fold, respectively. The model predictions of 254 μg/cm2/h and 24.6×10(-5) cm/h for MPG, and 202 μg/cm2/h and 19.8×10(-5) cm/h for DPG were in fairly good agreement with the measured values. Further, the model predicted a Jss of 101 μg/cm2/h and a Kp of 9.9×10(-5) cm/h for the homologue tripropylene glycol. Assuming that the measured Jss was the same under conditions of finite dose application (taken to be 10 μL/ cm2) and was maintained over a 24-h period (both conservative assumptions), the relative dermal absorption of the applied dose was estimated to be 23% (0.96%/h) for MPG and 9% (0.39%/h) for DPG. However, the extrapolation for MPG may be further overestimated due to possible residence in the stratum corneum under infinite conditions of exposure that would not be applicable to a finite loading dose.

摘要

未稀释的一缩二丙二醇(MPG)和二缩二丙二醇(DPG)在无限剂量应用条件下的人体腹部皮肤的体外透皮渗透已被测量,并与 SKINPERM QSAR 模型(ten Berge,2009 年)的预测进行了比较。MPG 和 DPG 的稳态渗透速率(Jss)分别为 97.6 和 39.3μg/cm2/h,渗透率系数(Kp)分别为 9.48×10(-5)cm/h 和 3.85×10(-5)cm/h。相比之下,SKINPERM 模型对 MPG 和 DPG 的 Jss 和 Kp 预测值分别高估了 2.6-5.1 倍。MPG 的模型预测值 254μg/cm2/h 和 24.6×10(-5)cm/h,DPG 的模型预测值 202μg/cm2/h 和 19.8×10(-5)cm/h 与测量值相当吻合。此外,该模型预测同系物三丙二醇的 Jss 为 101μg/cm2/h,Kp 为 9.9×10(-5)cm/h。假设在有限剂量应用条件下(取 10μL/cm2)测量的 Jss 相同,并且在 24 小时内保持不变(都是保守的假设),则施加剂量的相对皮肤吸收率估计为 MPG 的 23%(0.96%/h)和 DPG 的 9%(0.39%/h)。然而,由于在无限暴露条件下角质层中可能存在停留,MPG 的外推可能进一步高估,这在有限的加载剂量下是不适用的。

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