Pharmacokinetic/Pharmacodynamic Modeling of the Anti-Cancer Effect of Dexamethasone in Pancreatic Cancer Xenografts and Anticipation of Human Efficacious Doses
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作者:
Yao, Ye
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
Yao, Ye
[1
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Yao, Qingyu
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
Yao, Qingyu
[1
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Fu, Yu
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
Fu, Yu
[1
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Tian, Xiuyun
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机构:
Peking Univ Canc Hosp & Inst, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Dept Hepatopancreatobiliary Surg, Beijing 100142, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
Tian, Xiuyun
[2
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An, Qiming
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Peking Univ Canc Hosp & Inst, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Dept Hepatopancreatobiliary Surg, Beijing 100142, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
An, Qiming
[2
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Yang, Liang
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
Yang, Liang
[1
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Su, Hong
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
Su, Hong
[1
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Lu, Wei
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
Lu, Wei
[1
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Hao, Chunyi
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机构:
Peking Univ Canc Hosp & Inst, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Dept Hepatopancreatobiliary Surg, Beijing 100142, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
Hao, Chunyi
[2
]
Zhou, Tianyan
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
Zhou, Tianyan
[1
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机构:
[1] Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Dept Pharmaceut, Beijing 100191, Peoples R China
Dexamethasone (DEX), a synthetic glucocorticoid, exhibited anti-cancer efficacy in pancreatic xenografts derived from patient tumor tissue or cancer cell lines. The aim of this study was to establish pharmacokinetic/pharmacodynamic (PK/PD) models to quantitatively characterize the inhibitory effect of DEX on tumor growth as well as its discrepancy among 3 xenograft models. Data of tumor growth profiles were collected from a patient-derived xenograft (PDX) model in NOD/SCID mice and 2 cell line-derived (PANC-1 and SW1990) xenograft models in BALB/c nude mice. Empirical PK/PD models were developed to establish mathematical relationships between plasma concentration of DEX and tumor growth dynamics after integrating PK parameters extracted from literature. Drug effect in each model was well described by a linear inhibitory function with a potency factor of 4.67, 3.14, and 2.35 L/mg for PDX, PANC-1, and SW1990 xenograft, respectively. Human efficacious doses of DEX were preliminarily predicted through model-based simulation, and 60% tumor growth inhibition at clinical exposure corresponded to a daily dose range of 26-52 mg intravenously. This modeling work quantified the preclinical anti-cancer effect of DEX and demonstrated the feasibility of its medication in pancreatic cancer, which would be conductive to future translational research. (c) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
机构:
Inha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South KoreaInha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South Korea
Seo, Ju Hyeon
Jung, Kyung Hee
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Inha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South KoreaInha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South Korea
Jung, Kyung Hee
Son, Mi Kwon
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Inha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South KoreaInha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South Korea
Son, Mi Kwon
Yan, Hong Hua
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Inha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South KoreaInha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South Korea
Yan, Hong Hua
Ryu, Ye-Lim
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Inha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South KoreaInha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South Korea
Ryu, Ye-Lim
Kim, Jinhee
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Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South KoreaInha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South Korea
Kim, Jinhee
Lee, Jung Kyun
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Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea
Soomshinun Oriental Med Clin, Yongin 448170, Gyeonggi Do, South KoreaInha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South Korea
Lee, Jung Kyun
Hong, Sungwoo
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Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South KoreaInha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South Korea
Hong, Sungwoo
Hong, Soon-Sun
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Inha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South KoreaInha Univ, Dept Drug Dev, Coll Med, Inchon 400712, South Korea
机构:
Hop Rene Huguenin St Cloud, Inst Curie, Paris, FranceHop Rene Huguenin St Cloud, Inst Curie, Paris, France
Rezai, Keyvan
Urien, Saik
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Univ Paris 05, Sorbonne Paris Cite, AP HP, 0901 1CIC,Inserm Necker Cochin, Paris, France
Inst IMAGINE, Paris, FranceHop Rene Huguenin St Cloud, Inst Curie, Paris, France
Urien, Saik
Weill, Sophie
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Hop Rene Huguenin St Cloud, Inst Curie, Paris, FranceHop Rene Huguenin St Cloud, Inst Curie, Paris, France
Weill, Sophie
Barbin, Lise
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AB SCI, Paris, FranceHop Rene Huguenin St Cloud, Inst Curie, Paris, France
Barbin, Lise
Moussy, Alain
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AB SCI, Paris, FranceHop Rene Huguenin St Cloud, Inst Curie, Paris, France
Moussy, Alain
Lokiec, Francois
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Hop Rene Huguenin St Cloud, Inst Curie, Paris, FranceHop Rene Huguenin St Cloud, Inst Curie, Paris, France
机构:
Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China
Hao, Fangran
Wang, Siyuan
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China
Wang, Siyuan
Zhu, Xiao
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China
Zhu, Xiao
Xue, Junsheng
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China
Xue, Junsheng
Li, Jingyun
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China
Li, Jingyun
Wang, Lijie
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China
Wang, Lijie
Li, Jian
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China
Li, Jian
Lu, Wei
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机构:
Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China
Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China
Lu, Wei
Zhou, Tianyan
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Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China
Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R ChinaPeking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China