Blood partition and protein binding of a new neuroprotective agent for ischemia-reperfusion damage, KR-31378.
The blood partition of KR-31378 between plasma and blood cells and the factors influencing the binding of the drug to 4% human serum albumin (HSA) using an equilibrium dialysis technique were evaluated. KR-31378 reached an equilibrium rapidly between plasma and blood cells of rabbit blood. The equilibrium plasma/blood cells concentration ratios were independent of initial rabbit blood concentrations of KR-31378, 1, 10 and 50 microg/ml; the values were in the range of 1.42-2.33. It took approximately 12-h incubation to reach an equilibrium between plasma and isotonic Søresen phosphate buffer of pH 7.4 containing 3% dextran ('the buffer'). The binding of KR-31378 to 4% HSA was dependent on HSA concentrations (the binding values were 25.3 and 32.0% for HSA concentrations of 2 and 5%, respectively), incubation temperature (the binding values were 48.8, 29.0 and 25.8% for 4, 22 and 37 degrees C, respectively), pHs of isotonic Sørensen phosphate buffer containing 3% dextran (the binding values were 17.7, 20.6, 22.8, 25.6 and 29.5% for buffer pHs of 5.8, 6.4, 7.0, 7.4 and 8.0, respectively) and alpha-1-acid glycoprotein (AAG) concentrations (the binding values were 25.6, 29.9, 34.4 and 50.3% for AAG concentrations of 0, 0.08, 0.16 and 0.32%, respectively).
Lee
M H
MH
College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Kim
H J
HJ
Kim
S H
SH
Kim
S O
SO
Lee
D H
DH
Lim
H
H
Yoo
S E
SE
Lee
M G
MG
D000818:Animals; D004355:Drug Stability; D006146:Guanidines / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D011485:Protein Binding; D011714:Pyrans / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D011817:Rabbits; D012709:Serum Albumin / Q000378:metabolism*; D014018:Tissue Distribution
D006146:Guanidines; C438686:N''-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N'-benzylguanidine; D011714:Pyrans; D012709:Serum Albumin