Absorption, Distribution, Metabolism and Excretion (ADME) of Sorafenib and its two analogues of 2-aminoquinolone, in rat animal model, in silico – in vivo interplay

Year 2025, Volume: 29 Issue: 3, 1239 - 1247, 04.06.2025

Nasir Idkaidek , Hiba Saleh , Noor Wadi , Ahmad Alsheikh , Nidal Qinna , Ghaida Aldabet , Ayman Rabayia , Haya Tuffaha , Laith Alshoaibi , Ahmad Al-ghazawi

https://doi.org/10.12991/jrespharm.1633820

Abstract

The aim of this project is to synthesize Sorafenib two derivatives of 2-amino-6-phenoxyquinolone: AH1 & P64, then conduct ADME studies in healthy rats and correlate results with in vitro and in silico results. The absolute bioavailability of sorafenib derivatives were found very low 2.2 & 12 % for AH1 & P64 after in vivo oral and IV studies of the derivatives. Also, the relative bioavailability of sorafenib derivatives were found very low 0.3 & 0.6 % for AH1 & P64 after in vivo studies of sorafenib and its derivatives. In vitro stability tests showed stable derivatives in all degradation tests over the time course of the experiments which suggests stable derivatives in vivo too. However, in vitro diffusion study showed that derivatives permeability values are more than 60 times lower than sorafenib permeability which explains the low bioavailability of the derivatives as compared with sorafenib. Sorafenib derivatives were shown to have more in vitro anti-cancer activity, yet low in vivo bioavailability due to low intestinal permeability.

Keywords

ADME , ADMIT Lab , sorafenib , Pharmacokinetics

Ethical Statement

approved by the Research Committee at the Faculty of Pharmacy and Medical Sciences, University of Petra (Amman, Jordan) (E/A/8/2/2024

Supporting Institution

This research was supported by Petra University financial grant # 2-4-2023

Project Number

2-4-2023

Thanks

This research was supported by Petra University financial grant # 2-4-2023

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