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半生理药代动力学建模与模拟以评估OC-01（伐尼克兰）鼻喷雾剂的局部和全身药代动力学

Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal Spray.

作者信息

Wu Xiaofei, Zhang Fan, Yu Mengyang, Ding Faming, Luo Jinghui, Liu Bo, Li Yuan, Li Zhiping, Wang Hongyun

机构信息

Clinical Pharmacology Research Center, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Ji Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, China.

出版信息

Front Pharmacol. 2022 Jul 7;13:910629. doi: 10.3389/fphar.2022.910629. eCollection 2022.

DOI:10.3389/fphar.2022.910629
PMID:35873554
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9301199/
Abstract

This study aimed to build a nasal semi-physiologically based pharmacokinetic (PBPK) model to predict the intranasal pharmacokinetic (PK) of the OC-01(varenicline) nasal spray and accelerate the development of this drug. Based on the physiology of the human upper respiratory system, the semi-PBPK model was established and validated using systemic plasma PK data of varenicline previously observed in Americans and Chinese. Drug concentrations, both in respiratory tissue and plasma circulation system, were well simulated, and it was indicated that local concentration at the target site (nasal cavity) was significantly higher than that of plasma when OC-01 nasal spray was administered. The nasal semi-PBPK model successfully depicted the absorption and distribution of intranasal varenicline in the respiratory tissues and provided an alternative to clinical PK study of OC-01 nasal spray in Chinese. Meanwhile the current study presented a viable framework for predicting respiratory concentrations for other novel nasal spray drugs by semi-PBPK modeling.

摘要

本研究旨在构建一个基于鼻腔半生理药代动力学（PBPK）模型，以预测OC-01（伐尼克兰）鼻喷雾剂的鼻内药代动力学（PK），并加速该药物的研发。基于人类上呼吸道的生理学，利用先前在美国人和中国人中观察到的伐尼克兰的全身血浆PK数据，建立并验证了半PBPK模型。呼吸组织和血液循环系统中的药物浓度均得到了良好模拟，结果表明，给予OC-01鼻喷雾剂时，靶部位（鼻腔）的局部浓度显著高于血浆浓度。该鼻腔半PBPK模型成功地描绘了鼻内伐尼克兰在呼吸组织中的吸收和分布情况，并为中国人群中OC-01鼻喷雾剂的临床PK研究提供了一种替代方法。同时，本研究为通过半PBPK建模预测其他新型鼻喷雾剂药物的呼吸道浓度提供了一个可行的框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d51/9301199/8afc67765240/fphar-13-910629-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d51/9301199/b8e6356110ee/fphar-13-910629-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d51/9301199/1ca63f58ac4f/fphar-13-910629-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d51/9301199/1aea760c27ad/fphar-13-910629-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d51/9301199/8afc67765240/fphar-13-910629-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d51/9301199/c8cb4849f2eb/fphar-13-910629-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d51/9301199/a67ae2b90c05/fphar-13-910629-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d51/9301199/e54af5010dd7/fphar-13-910629-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d51/9301199/1ca63f58ac4f/fphar-13-910629-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d51/9301199/8afc67765240/fphar-13-910629-g009.jpg

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