• DOI:10.1248/CPB.32.3155
• Corpus ID: 27231856

Binding of hydralazine and a major metabolite, pyruvate hydrazone, to rat plasma protein and human serum albumin.

@article{Ogiso1984BindingOH,
  title={Binding of hydralazine and a major metabolite, pyruvate hydrazone, to rat plasma protein and human serum albumin.},
  author={Taro Ogiso and Masahiro Iwaki},
  journal={Chemical \& pharmaceutical bulletin},
  year={1984},
  volume={32 8},
  pages={
          3155-63
        }
}

• T. Ogiso, M. Iwaki
• Published 25 August 1984
• Biology, Chemistry
• Chemical & pharmaceutical bulletin

The interaction of hydralazine (HP) and a major metabolite, pyruvate hydrazone (HPH), with rat plasma protein or human serum albumin (HSA) was studied both in vivo (by the ultrafiltration method) and in vitro (at 20 and 30°C, by the equilibrium dialysis method). The binding of HP and HPH to plasma proteins was fairly high (96.0 and 81.7%. respectively) after i.v. administration to rats. HPH, which had an association constant higher than HP, was found to interact with a single class of site on HSA, while HP was bound to at least two heterogeneous binding sites. The interaction between HP and rat plasma protein or HSA was temperaturedependent at the secondary binding site, suggesting that a nonionic mechanism is involved in the binding, and the interaction at the primary site was ionic strength-dependent. In contrast, the interaction of HPH with HSA showed less temperature-dependence. The thermodynamic analyses of the HP binding process at the secondary site showed a negative value for ΔG°, a large contribution of ΔH° to ΔG° and a positive ΔS°, while at the primary site a large contribution to ΔG° by ΔS° was seen. Thus, these findings suggest that the main binding energies at the primary and secondary sites are derived from electrostatic and nonionic sources, respectively. For HPH binding, however, the predominantly bound species was ionic. HP did not induce competitive displacement of fluorescent probes except for a slight displacement of dansylamide in the presence of a high concentration of HP. This suggests that HP is bound weakly to sites other than sites I and II, two specific sites for acidic drugs, on HSA. The present results lead us to postulate that HP interacts with the receptor sites mainly by hydrophobic and hydrogen bonding forces and partly by electrostatic forces.