Physiologically based pharmacokinetic modeling of the disposition of octamethylcyclotetrasiloxane (D4) migration from implants in humans

被引：0
作者：
Thrall, Karla [1 ]
Soelberg, Jolen J. [1 ]
Powell, Thomas E. [2 ]
Corley, Richard A. [1 ]
机构：
[1] Battelle, Pacific Northwest Division, Mail Stop P7-59, Richland, WA 99354-1793
[2] Allergan Medical, Santa Barbara, CA
来源：
Journal of Long-Term Effects of Medical Implants | 2008年 / 18卷 / 02期
关键词：
D4; Implants; Migration; PBPK; Silicone;
D O I：
10.1615/JLongTermEffMedImplants.v18.i2.20
中图分类号：
学科分类号：
摘要：
A physiologically based pharmacokinetic model was developed to describe the silicone constituent octamethylcyclotetrasiloxane (D4) and its migration from intact or ruptured silicone gel-filled breast implants into surrounding tissues. D4 is a representative low-molecular weight constituent of silicone gel that is soluble enough in biological fluids to migrate from the implant and into surrounding tissues. The simulations were based on a representative young adult (premenopausal) woman and a mature (postmenopausal) woman using worst-case exposure conditions (i.e., complete rupture of the largest implant available, maximum levels of D4 in silicone, equal solubility of D4 in breast tissue and gel, and a range of breast tissue fat contents). The results indicate that D4 is cleared primarily by exhalation with highest concentrations achieved briefly in breast tissues of a representative postmenopausal woman. Maximum D4 levels in breast tissues for this scenario were estimated to be approximately 750 ppb with over 90 cleared in about 20 days. Thus, it is unlikely that D4 would be detected in any tissue within a few weeks of receiving an implant, even if immediately ruptured, under the assumptions used in this model. © 2008 by Begell House, Inc.
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页码：133 / 144
页数：11
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