Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human

Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human

Physiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) models can contribute to animal-to-human extrapolation and therapeutic dose predictions. Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran have been completed. In this paper, a potentially effective dose...

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Main Authors: Fen Yang, Baolian Wang, Zhihao Liu, Xuejun Xia, Weijun Wang, Dali Yin, Li Sheng, Yan Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-10-01
Series:Frontiers in Pharmacology
Subjects:
buagafuran
pharmacokinetics
pharmacodynamic
physiologically based pharmacokinetic (PBPK) modeling
in silico modeling
clinical pharmacokinetics
Online Access:http://journal.frontiersin.org/article/10.3389/fphar.2017.00683/full
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spelling doaj-4a58e6dc23304c06b7b0375b33296bd32020-11-24T23:00:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-10-01810.3389/fphar.2017.00683296308Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and HumanFen Yang0Fen Yang1Baolian Wang2Zhihao Liu3Xuejun Xia4Weijun Wang5Dali Yin6Li Sheng7Yan Li8Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Center of Drug Clinical Trial, Peking University Cancer Hospital and Institute, Beijing, ChinaClinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Drug Delivery System, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Synthetic Medicinal Chemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaPhysiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) models can contribute to animal-to-human extrapolation and therapeutic dose predictions. Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran have been completed. In this paper, a potentially effective dose for buagafuran of 30 mg t.i.d. in human was estimated based on the human brain concentration predicted by a PBPK/PD modeling. The software GastroPlusTM was used to build the PBPK/PD model for buagafuran in rat which related the brain tissue concentrations of buagafuran and the times of animals entering the open arms in the pharmacological model of elevated plus-maze. Buagafuran concentrations in human plasma were fitted and brain tissue concentrations were predicted by using a human PBPK model in which the predicted plasma profiles were in good agreement with observations. The results provided supportive data for the rational use of buagafuran in clinic.http://journal.frontiersin.org/article/10.3389/fphar.2017.00683/fullbuagafuranpharmacokineticspharmacodynamicphysiologically based pharmacokinetic (PBPK) modelingin silico modelingclinical pharmacokinetics
collection DOAJ
language English
format Article
sources DOAJ
author Fen Yang
Fen Yang
Baolian Wang
Zhihao Liu
Xuejun Xia
Weijun Wang
Dali Yin
Li Sheng
Yan Li
spellingShingle Fen Yang
Fen Yang
Baolian Wang
Zhihao Liu
Xuejun Xia
Weijun Wang
Dali Yin
Li Sheng
Yan Li
Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human
Frontiers in Pharmacology
buagafuran
pharmacokinetics
pharmacodynamic
physiologically based pharmacokinetic (PBPK) modeling
in silico modeling
clinical pharmacokinetics
author_facet Fen Yang
Fen Yang
Baolian Wang
Zhihao Liu
Xuejun Xia
Weijun Wang
Dali Yin
Li Sheng
Yan Li
author_sort Fen Yang
title Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human
title_short Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human
title_full Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human
title_fullStr Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human
title_full_unstemmed Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human
title_sort prediction of a therapeutic dose for buagafuran, a potent anxiolytic agent by physiologically based pharmacokinetic/pharmacodynamic modeling starting from pharmacokinetics in rats and human
publisher Frontiers Media S.A.
series Frontiers in Pharmacology
issn 1663-9812
publishDate 2017-10-01
description Physiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) models can contribute to animal-to-human extrapolation and therapeutic dose predictions. Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran have been completed. In this paper, a potentially effective dose for buagafuran of 30 mg t.i.d. in human was estimated based on the human brain concentration predicted by a PBPK/PD modeling. The software GastroPlusTM was used to build the PBPK/PD model for buagafuran in rat which related the brain tissue concentrations of buagafuran and the times of animals entering the open arms in the pharmacological model of elevated plus-maze. Buagafuran concentrations in human plasma were fitted and brain tissue concentrations were predicted by using a human PBPK model in which the predicted plasma profiles were in good agreement with observations. The results provided supportive data for the rational use of buagafuran in clinic.
topic buagafuran
pharmacokinetics
pharmacodynamic
physiologically based pharmacokinetic (PBPK) modeling
in silico modeling
clinical pharmacokinetics
url http://journal.frontiersin.org/article/10.3389/fphar.2017.00683/full
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