Khotimchenko Maksim, Antontsev Victor, Chakravarty Kaushik, Hou Hypatia, Varshney Jyotika
VeriSIM Life Inc., 1 Sansome St, Suite 3500, San Francisco, CA 94104, USA.
Pharmaceutics. 2021 Feb 21;13(2):284. doi: 10.3390/pharmaceutics13020284.
The use of opioid analgesics in treating severe pain is frequently associated with putative adverse effects in humans. Topical agents that are shown to have high efficacy with a favorable safety profile in clinical settings are great alternatives for pain management of multimodal analgesia. However, the risk of side effects induced by transdermal absorption and systemic exposure is of great concern as they are challenging to predict. The present study aimed to use "BIOiSIM" an artificial intelligence-integrated biosimulation platform to predict the transdermal disposition of opioid analgesics. The model successfully predicted their exposure following the topical application of central opioid agonist buprenorphine and peripheral agonist oxycodone in healthy human subjects with simulation of intra-skin exposure in subjects with burns and pressure wounds. The predicted plasma levels of analgesics were used to evaluate the safety of the therapeutic pain control in patients with the dermal structural impairments caused by acute (burns) or chronic cutaneous lesions (pressure wounds) with topical opioid analgesics.
在治疗重度疼痛时使用阿片类镇痛药常常与人类潜在的不良反应相关。在临床环境中显示出高效且安全性良好的局部用药是多模式镇痛疼痛管理的极佳替代方案。然而，经皮吸收和全身暴露所引发的副作用风险备受关注，因为这些副作用难以预测。本研究旨在使用“BIOiSIM”——一个集成人工智能的生物模拟平台来预测阿片类镇痛药的经皮处置情况。该模型成功预测了在健康人类受试者局部应用中枢阿片类激动剂丁丙诺啡和外周激动剂羟考酮后的暴露情况，并模拟了烧伤和压疮患者的皮肤内暴露。预测的镇痛药血浆水平用于评估局部使用阿片类镇痛药对急性（烧伤）或慢性皮肤损伤（压疮）导致皮肤结构受损患者进行治疗性疼痛控制的安全性。
