Identification of System Independent and Dependent Parameters for Reliable in vitro-in vivo Extrapolation of P-glycoprotein using a Mass Action Kinetic Model

2021 ◽  
Author(s):  
Zhou Meng
Keyword(s):  
Kinetic Model ◽  
Mass Action ◽  
Mass Action Kinetic ◽  
P Glycoprotein ◽  
In Vivo Extrapolation

Quantitative In Vitro-to-In Vivo Extrapolation: Nominal versus Freely Dissolved Concentration

2021 ◽  
Vol 34 (4) ◽  
pp. 1175-1182
Author(s):  
Luise Henneberger ◽  
Julia Huchthausen ◽  
Niklas Wojtysiak ◽  
Beate I. Escher
Keyword(s):  
Freely Dissolved Concentration ◽  
In Vivo Extrapolation

scholarly journals Towards a generic physiologically based kinetic model to predict in vivo uterotrophic responses in rats by reverse dosimetry of in vitro estrogenicity data

2017 ◽  
Vol 92 (3) ◽  
pp. 1075-1088 ◽  
Author(s):  
Mengying Zhang ◽  
Bennard van Ravenzwaay ◽  
Eric Fabian ◽  
Ivonne M. C. M. Rietjens ◽  
Jochem Louisse
Keyword(s):  
Kinetic Model ◽  
Reverse Dosimetry ◽  
Physiologically Based

scholarly journals Overcoming multidrug-resistance in vitro and in vivo using the novel P-glycoprotein inhibitor 1416

2012 ◽  
Vol 32 (6) ◽  
pp. 559-566 ◽  
Author(s):  
Yan Xu ◽  
Feng Zhi ◽  
Guangming Xu ◽  
Xiaolei Tang ◽  
Sheng Lu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Chemotherapy ◽  
Antitumour Activity ◽  
Multidrug Resistant ◽  
The Novel ◽  
Mice Model ◽  
P Glycoprotein ◽  
Channel Currents

MDR (multidrug-resistance) represents a major obstacle to successful cancer chemotherapy and is usually accomplished by overexpression of P-gp (P-glycoprotein). Much effort has been devoted to developing P-gp inhibitors to modulate MDR. However, none of the inhibitors on the market have been successful. 1416 [1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride (phenoprolamine hydrochloride)] is a new VER (verapamil) analogue with a higher IC50 for blocking calcium channel currents than VER. In the present paper, we examined the inhibition effect of 1416 on P-gp both in vitro and in vivo. 1416 significantly enhanced cytotoxicity of VBL (vinblastine) in P-gp-overexpressed human multidrug-resistant K562/ADM (adriamycin) and KBV cells, but had no such effect on the parent K562 and KB cells. The MDR-modulating function of 1416 was further confirmed by increasing intracellular Rh123 (rhodanmine123) content in MDR cells. Human K562/ADM xenograft-nude mice model verified that 1416 potentiates the antitumour activity of VBL in vivo. RT-PCR (reverse transcriptase-PCR) and FACS analysis demonstrated that the expression of MDR1/P-gp was not affected by 1416 treatment. All these observations suggest that 1416 could be a promising agent for overcoming MDR in cancer chemotherapy.

In Vitro and in Vivo Evaluation of Phenylbutenoid Dimers as Inhibitors of P-Glycoprotein

2013 ◽  
Vol 76 (12) ◽  
pp. 2277-2281 ◽  
Author(s):  
Song Wha Chae ◽  
Ah-Reum Han ◽  
Jung Hyun Park ◽  
Jeong Yeon Rhie ◽  
Hee-Jong Lim ◽  
...  
Keyword(s):  
In Vivo Evaluation ◽  
P Glycoprotein

scholarly journals Upregulations of Clcn3 and P-Gp Provoked by Lens Osmotic Expansion in Rat Galactosemic Cataract

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Lixia Ji ◽  
Lixia Cheng ◽  
Zhihong Yang
Keyword(s):  
Osmotic Stress ◽  
Early Stage ◽  
Lens Epithelial Cells ◽  
Anterior Capsule ◽  
Glycoprotein P ◽  
Protein Levels ◽  
P Glycoprotein ◽  
Sugar Cataract

Objective.Lens osmotic expansion, provoked by overactivated aldose reductase (AR), is the most essential event of sugar cataract. Chloride channel 3 (Clcn3) is a volume-sensitive channel, mainly participating in the regulation of cell fundamental volume, and P-glycoprotein (P-gp) acts as its modulator. We aim to study whether P-gp and Clcn3 are involved in lens osmotic expansion of galactosemic cataract.Methods and Results.In vitro, lens epithelial cells (LECs) were primarily cultured in gradient galactose medium (10–60 mM), more and more vacuoles appeared in LEC cytoplasm, and mRNA and protein levels of AR, P-gp, and Clcn3 were synchronously upregulated along with the increase of galactose concentration. In vivo, we focused on the early stage of rat galactosemic cataract, amount of vacuoles arose from equatorial area and scattered to the whole anterior capsule of lenses from the 3rd day to the 9th day, and mRNA and protein levels of P-gp and Clcn3 reached the peak around the 9th or 12th day.Conclusion. Galactosemia caused the osmotic stress in lenses; it also markedly leads to the upregulations of AR, P-gp, and Clcn3 in LECs, together resulting in obvious osmotic expansion in vitro and in vivo.

Sign in / Sign up

Export Citation Format

Share Document