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

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

Makale detayları

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

Yazarlar:

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

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences (Other)

Dergi:

Journal of Research in Pharmacy Vol.29 Issue 3, pp.1239-1247

Belge Tipi:

Makale

Yayın Tarihi:

4/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001344592

pISSN:

2630-6344

Anahtar kelimeler:

Özet:

 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.

 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.

 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.

 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.

Makale detayları

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

Yazarlar:

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

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences (Other)

Dergi:

Journal of Research in Pharmacy Vol.29 Issue 3, pp.1239-1247

Belge Tipi:

Makale

Yayın Tarihi:

4/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001344592

pISSN:

2630-6344

ADME

ADMIT Lab

sorafenib

Pharmacokinetics

Sayı

Makale detayları

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

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

Yayıncı: Marmara University

Ana Başlıklar: Pharmacology and Pharmaceutical Sciences (Other)

Dergi: Journal of Research in Pharmacy Vol.29 Issue 3, pp.1239-1247

Belge Tipi: Makale

Yayın Tarihi: 4/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001344592

pISSN: 2630-6344

ADME

ADMIT Lab

sorafenib

Pharmacokinetics

Sayı

Yazarlar:

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

Yayıncı:

Marmara University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences (Other)

Dergi:

Journal of Research in Pharmacy Vol.29 Issue 3, pp.1239-1247

Belge Tipi:

Makale

Yayın Tarihi:

4/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001344592

pISSN:

2630-6344