TY  - JOUR
T1  - Absorption, Distribution, Metabolism and Excretion (ADME) of Sorafenib and its two analogues of 2-aminoquinolone, in rat animal model, in silico – in vivo interplay
AU  - Idkaidek, Nasir
AU  - Saleh, Hiba
AU  - Wadi, Noor
AU  - Alsheikh, Ahmad
AU  - Qinna, Nidal
AU  - Aldabet, Ghaida
AU  - Rabayia, Ayman
AU  - Tuffaha, Haya
AU  - Alshoaibi, Laith
AU  - Al-ghazawi, Ahmad
PY  - 2025
DA  - June
Y2  - 2025
DO  - 10.12991/jrespharm.1633820
JF  - Journal of Research in Pharmacy
JO  - J. Res. Pharm.
PB  - Marmara University
WT  - DergiPark
SN  - 2630-6344
SP  - 1239
EP  - 1247
VL  - 29
IS  - 3
LA  - en
AB  - 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.
KW  - ADME
KW  - ADMIT Lab
KW  - sorafenib
KW  - Pharmacokinetics
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UR  - https://doi.org/10.12991/jrespharm.1633820
L1  - https://dergipark.org.tr/en/download/article-file/4582387
ER  -