Factors influencing the protein binding of a new phosphodiesterase V inhibitor, DA-8159, using an equilibrium dialysis technique

• Published in: Biopharmaceutics & drug disposition Vol. 21; no. 7; pp. 285 - 291
• Main Authors: Shim, Hyun J., Lee, Eun J., Kim, So H., Kim, Soon H., Yoo, Moohi, Kwon, Jong W., Kim, Won B., Lee, Myung G.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-10-2000; Wiley
• Subjects: and humans; Animals; Biological and medical sciences; Buffers; Chromatography, High Pressure Liquid; DA-8159; Dialysis - methods; dogs; equilibrium dialysis; factors influencing protein binding; Heparin - metabolism; Humans; Hydrogen-Ion Concentration; Medical sciences; Miscellaneous; Molecular Structure; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - metabolism; Phosphodiesterase Inhibitors - pharmacokinetics; Protein Binding; Pyrimidines; rabbits; rats; rats, rabbits, dogs, and humans; Serum Albumin - metabolism; Sulfonamides; Temperature; Human; Fissipedia; Carnivora; Rat; Enzyme; 3',5'-Cyclic-GMP phosphodiesterase; Rodentia; Enzyme inhibitor; Rabbit; Esterases; Serum albumin; Phosphoric diester hydrolases; Lagomorpha; In vitro; Protein; Blood plasma; Vertebrata; Biological fixation; Mammalia; Hydrolases; Dog; Equilibrium dialysis
• ISSN: 0142-2782; 1099-081X
• DOI: 10.1002/bdd.238

Various factors influencing the protein binding of DA‐8159 to 4% human serum albumin (HSA) were evaluated using an equilibrium dialysis technique at an initial DA‐8159 concentration of 5 µg/mL. It took approximately 8 h incubation to reach an equilibrium between 4% HSA and an isotonic phosphate buffer of pH 7.4 containing 3% of dextran (‘the buffer’) using a Spectra/Por 2 membrane (mol. wt. cut‐off: 12 000–14 000) in a water bath shaker kept at 37°C and at a rate of 50 oscillations per min. The extent of binding was dependent on DA‐8159 concentrations, HSA concentrations, incubation temperature, buffer pH, and alpha‐1‐acid glycoprotein (AAG) concentrations. The binding of DA‐8159 in heparinized human plasma (93.9%) was significantly higher than in rats (81.4%), rabbits (80.4%), and dogs (82.2%), and this could be due to differences in AAG concentrations in plasma. Copyright © 2000 John Wiley & Sons, Ltd.