Cremophor EL Alters the Plasma Protein Binding and Pharmacokinetic Profile of Valspodar in Rats

Drug Research ◽  
2017 ◽  
Vol 67 (10) ◽  
pp. 591-595
Author(s):  
Ziyad Binkhathlan
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Pharmaceutical Formulations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Cremophor El ◽  
Unbound Fraction ◽  
Peg 400

AbstractCremophor EL is a nonionic surfactant widely used in pharmaceutical formulations. Nonetheless, there are several reports on the influence of this excipient on the protein binding, pharmacokinetics, and pharmacodynamics of drugs. Valspodar is an investigational non-immunosuppressive derivative of cyclosporine A, used in clinical trials for treatment of multidrug resistant tumors. The formulation of valspodar (Amdray®) contains cremophor EL and ethanol as solubilizing agents. The main aim of the current study was to assess the plasma protein binding (in vitro) and the pharmacokinetic profile of valspodar in the cremophor EL-based formulation in comparison to a cremophor EL-free formulation following intravenous (i. v.) administration to rats. Valspodar dissolved in PEG 400/ethanol (diluted in Dextrose 5%) was used as the cremophor EL-free formulation. The in vitro plasma unbound fraction (f u) of valspodar in the cremophor EL formulation was 2.3-fold higher than the PEG 400/ethanol formulation. Following a single i. v. dose of 5 mg/kg, valspodar in the cremophor EL-based formulation had around 50% lower plasma AUC compared to the PEG 400/ethanol formulation. Moreover, the cremophor EL formulation had significantly higher volume of distribution and clearance in comparison to the PEG 400-based formulation. The results highlight the significance of excipient-drug interaction that should not be overlooked during the early stages of drug development.

scholarly journals Metabolism and plasma protein binding of 16 straight- and branched-chain parabens in in vitro liver and skin models

2020 ◽  
pp. 105051
Author(s):  
Cathy Lester ◽  
Nicola J. Hewitt ◽  
Ursula Müller-Vieira ◽  
Manuela Mayer ◽  
Corie Ellison ◽  
...  
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Branched Chain

Prediction of drug-drug interaction from In vitro plasma protein binding and metabolism

1981 ◽  
Vol 30 (24) ◽  
pp. 3347-3354 ◽  
Author(s):  
Osamu Sugita ◽  
Yasufumi Sawada ◽  
Yuichi Sugiyama ◽  
Tatsuji Iga ◽  
Manabu Hanano
Keyword(s):  
Drug Interaction ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Drug Drug Interaction

Evaluation of oral pharmacokinetics, in vitro metabolism, blood partitioning and plasma protein binding of novel antidiabetic agent, S009-0629 in rats

2018 ◽  
Vol 79 (4) ◽  
pp. 173-183 ◽  
Author(s):  
Guru Raghavendra Valicherla ◽  
Kishan Shamjibhai Italiya ◽  
Chandra Prakash Gupta ◽  
Shachi Mishra ◽  
Mohammed Riyazuddin ◽  
...  
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
In Vitro Metabolism ◽  
Antidiabetic Agent ◽  
Oral Pharmacokinetics

scholarly journals Gallium-68-Labelled Indocyanine Green as a Potential Liver Reserve Imaging Agent

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Yuxiao Xia ◽  
Li Zhang ◽  
Yanhong Zhao ◽  
Xiangdong Liu ◽  
Liang Cai ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Water Solubility ◽  
Time Points ◽  
Binding Rate ◽  
Very High

Objective. This work evaluated the potential of 68Ga-labelledNOTA-ICG (1,4,7-triazacyclononane-1,4,7-triacetic acid indocyanine green) for liver reserve imaging. Methods. To determine the optimal conditions for generating 68Ga-NOTA-ICG, various reaction parameters were implemented. Quality control analysis was performed using different chromatography techniques. The in vitro and in vivo stability was also measured at specific time points. The radioactivity ratio between n-octanol and water was determined to evaluate the water solubility of 68Ga-NOTA-ICG. The plasma-protein binding rate of the labelled compound was determined by the methanol method. The biodistribution and imaging findings were evaluated in normal animals at different time points after injection. A preliminary imaging evaluation was performed using an animal model of hepatic ischaemia-reperfusion injury, which was confirmed by pathology. Results. 68Ga-NOTA-ICG was prepared with very high radiochemical purity (>98%) by reacting at 90°C for 10 min at pH = 3.5∼4.0, with excellent stability in vivo and in vitro (>95% 3 h postpreparation). The in vitro plasma-protein binding rate of 68Ga-NOTA-ICG was 13.01 ± 0.7%, and it showed strong water solubility log P=−2.01±0.04. We found that in addition to excretion through the biliary tract and intestines, 68Ga-NOTA-ICG can be excreted through the urinary tract. The image quality of 68Ga-NOTA-ICG was very high; imaging agent retained in the area of liver injury could clearly be observed. Conclusion. This is the first report on a 68Ga-labelled NOTA-ICG fragment for liver reserve function studies. This complex has promise as a candidate agent for liver reserve imaging.

Sign in / Sign up

Export Citation Format

Share Document