Bioavailability, plasma protein binding and metabolic stability studies of a ALDH2 activator, alda-1, using a validated LC-ESI-MS/MS method in rat plasma

RSC Advances ◽  
2015 ◽  
Vol 5 (67) ◽  
pp. 54395-54402 ◽  
Author(s):  
Isha Taneja ◽  
Kanumuri Siva Rama Raju ◽  
Monika Mittal ◽  
Kapil Dev ◽  
Mohammad Faheem Khan ◽  
...  
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Rat Plasma ◽  
Metabolic Stability ◽  
Stability Studies ◽  
Esi Ms

Alda-1 was found to be a poorly bioavailable, 82–86% protein bound, high extraction compound.

Roflumilast analogs with improved metabolic stability, plasma protein binding, and pharmacokinetic profile

2019 ◽  
Vol 11 (6) ◽  
pp. 886-897 ◽  
Author(s):  
Bahia A. Moussa ◽  
Asmaa A. El‐Zaher ◽  
Mohamed K. El‐Ashrey ◽  
Marwa A. Fouad
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Pharmacokinetic Profile ◽  
Metabolic Stability

scholarly journals Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 339
Author(s):  
Guru R. Valicherla ◽  
Roshan A. Katekar ◽  
Shailesh Dadge ◽  
Mohammed Riyazuddin ◽  
Anees A. Syed ◽  
...  
Keyword(s):  
Gender Difference ◽  
Protein Binding ◽  
Blood Plasma ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Liver Microsomes ◽  
Rat Plasma ◽  
Dose Proportionality

PSTi8 is a pancreastatin inhibitory peptide that is effective in the treatment of diabetic models. This study investigates the pharmacokinetic (PK) properties of PSTi8 in Sprague Dawley rats, for the first time. In vitro and in vivo PK studies were performed to evaluate the solubility, stability in plasma and liver microsomes, plasma protein binding, blood–plasma partitioning, bioavailability, dose proportionality, and gender difference in PK. Samples were analyzed using the validated LC-MS/MS method. The solubility of PSTi8 was found to be 9.30 and 25.75 mg/mL in simulated gastric and intestinal fluids, respectively. The protein binding of PSTi8 was estimated as >69% in rat plasma. PSTi8 showed high stability in rat plasma and liver microsomes and the blood–plasma partitioning was >2. The bioavailability of PSTi8 after intraperitoneal and subcutaneous administration was found to be 95.00 ± 12.15 and 78.47 ± 17.72%, respectively, in rats. PSTi8 showed non-linear PK in dose proportionality studies, and has no gender difference in the PK behavior in rats. The high bioavailability of PSTi8 can be due to high water solubility and plasma protein binding, low clearance and volume of distribution. Our in vitro and in vivo findings support the development of PSTi8 as an antidiabetic agent.

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