Factors influencing the protein binding of a new phosphodiesterase V inhibitor, DA-8159, using an equilibrium dialysis technique.
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 microg/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 degrees 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.
Shim
H J
HJ
College of Pharmacy, Seoul National University, Kwanak-Gu, Seoul, Republic of Korea.
Lee
E J
EJ
Kim
S H
SH
Kim
S H
SH
Yoo
M
M
Kwon
J W
JW
Kim
W B
WB
Lee
M G
MG
D000818:Animals; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis / Q000379:methods*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D011485:Protein Binding; D011743:Pyrimidines; D012709:Serum Albumin / Q000378:metabolism*; D013449:Sulfonamides; D013696:Temperature; D000096926:Benzenesulfonamides
D002021:Buffers; D006493:Heparin; D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D012709:Serum Albumin; D013449:Sulfonamides; C419664:udenafil; D000096926:Benzenesulfonamides