Stability, blood partition and protein binding of an antifibrotic agent, oltipraz.
The stability, blood partition and factors influencing the binding of oltipraz to 4% human serum albumin (HSA) were evaluated. Oltipraz was relatively stable in various pH (1-12) solutions for up to 48-h incubation, however, it was unstable in pH 13 solution and rat plasma and urine. Oltipraz reached an equilibrium fast (within 30 s mixing manually) between plasma and blood cells o f rabbit blood and the plasma-to-blood cells concentration ratios were independent of initial blood concentrations of oltipraz, 1 and 5 microg/ml; the ratios ranged from 0.908 to 1.004. The binding of oltipraz to 4% HSA was independent of oltipraz concentrations ranging from 1 to 100 microg/ml using an equilibrium dialysis technique: the mean value was 95.0%. However, the binding of oltipraz was dependent on HSA concentrations (the low concentrations, 3, 2, 1 and 0.5% of HSA caused an increase in the unbound fraction of oltipraz by 1.32, 1.98, 3.44 and 5.31 times, respectively, compared with the mean value from 4-6% HSA), incubation temperature (the unbound fractions at 37 degrees C and 22 degrees C increased 1.89 and 1.73 times, respectively, than that at 4 degrees C) and the buffer pHs (the unbound fractions were 6.36, 6.51, 5.60 and 4.63% for buffer pHs of 5.8, 6.4, 7.4 and 8.0, respectively).
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College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Kim
E J
EJ
Kim
S H
SH
Kim
S G
SG
Lee
M G
MG
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D011485:Protein Binding; D011719:Pyrazines / Q000097:blood / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D012556:Schistosomicides / Q000097:blood / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*; D013871:Thiones; D013876:Thiophenes
D011719:Pyrazines; D012556:Schistosomicides; D012709:Serum Albumin; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz