Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal Spray
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 mod...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.910629/full |
| _version_ | 1818113250282176512 |
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| author | Xiaofei Wu Fan Zhang Mengyang Yu Faming Ding Jinghui Luo Bo Liu Yuan Li Zhiping Li Hongyun Wang |
| author_facet | Xiaofei Wu Fan Zhang Mengyang Yu Faming Ding Jinghui Luo Bo Liu Yuan Li Zhiping Li Hongyun Wang |
| author_sort | Xiaofei Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T03:31:51Z |
| format | Article |
| id | doaj.art-bd5eeca28c0e456fa3b7df6b19ea79d6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T03:31:51Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-bd5eeca28c0e456fa3b7df6b19ea79d62022-12-22T01:22:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.910629910629Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal SprayXiaofei Wu0Fan Zhang1Mengyang Yu2Faming Ding3Jinghui Luo4Bo Liu5Yuan Li6Zhiping Li7Hongyun Wang8Clinical 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, ChinaClinical 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, ChinaClinical 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, ChinaJi Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, ChinaJi Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, ChinaJi Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, ChinaJi Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, ChinaJi Xing Pharmaceuticals (Shanghai) Co., Ltd., Shanghai, ChinaClinical 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, ChinaThis 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.910629/fullnasal sprayvareniclineOC-01dry eye diseasepharmacokineticssemi-PBPK model |
| spellingShingle | Xiaofei Wu Fan Zhang Mengyang Yu Faming Ding Jinghui Luo Bo Liu Yuan Li Zhiping Li Hongyun Wang Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal Spray Frontiers in Pharmacology nasal spray varenicline OC-01 dry eye disease pharmacokinetics semi-PBPK model |
| title | Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal Spray |
| title_full | Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal Spray |
| title_fullStr | Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal Spray |
| title_full_unstemmed | Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal Spray |
| title_short | Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal Spray |
| title_sort | semi pbpk modeling and simulation to evaluate the local and systemic pharmacokinetics of oc 01 varenicline nasal spray |
| topic | nasal spray varenicline OC-01 dry eye disease pharmacokinetics semi-PBPK model |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.910629/full |
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