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

• Main Authors: Fen Yang (Author), Baolian Wang (Author), Zhihao Liu (Author), Xuejun Xia (Author), Weijun Wang (Author), Dali Yin (Author), Li Sheng (Author), Yan Li (Author)
• Format: Book
• Published: Frontiers Media S.A., 2017-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1663-9812
10.3389/fphar.2017.00683