Interaction of Aripiprazole With Human α1-Acid Glycoprotein
| Autor: | Koji Nishi, Mai Hashimoto, Shuhei Imoto, Masaki Otagiri, Hiroshi Morioka, Keiki Sakurama, Keishi Yamasaki, Nagiko Udo, Yoshihiro Kobashigawa |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
chemistry.chemical_classification
Circular dichroism Albumin Pharmaceutical Science Isothermal titration calorimetry Human albumin 02 engineering and technology 021001 nanoscience & nanotechnology 030226 pharmacology & pharmacy Blood proteins 03 medical and health sciences 0302 clinical medicine Biochemistry chemistry Pharmacokinetics medicine Aripiprazole 0210 nano-technology Glycoprotein medicine.drug |
| Zdroj: | Journal of Pharmaceutical Sciences. 108:3911-3916 |
| ISSN: | 0022-3549 |
| Popis: | We recently reported that aripiprazole binds strongly to human albumin. In continuing our investigations, we investigated the mechanism responsible for the binding and the related interactions of aripiprazole with α1-acid glycoprotein (AGP). The extrinsic Cotton effects for the binding of aripiprazole and its derivatives to AGP were generated, but the magnitudes of the induced circular dichroism intensities did not correlate with those for the binding affinities. It therefore appears that the binding mode of aripiprazole with AGP is somewhat complicated, compared with that of albumin. Isothermal titration calorimetry data obtained for the binding of aripiprazole with AGP were different from that for albumin systems in that the 3 driving reactions, entropy-driven, enthalpy-driven, and the entropy-enthalpy mixed type, were all found for the AGP system, but not albumin. Moreover, the weak binding mode of aripiprazole with the 2 proteins were supported by a molecular docking model analysis. The concentration of albumin in plasma is about 50 times higher than those of AGP, but AGP levels in plasma are increased by about 10 times under inflammatory disease. Therefore, the involvement of these 2 plasma proteins should be considered in more depth for understanding the pharmacokinetics of aripiprazole. |
| Databáze: | OpenAIRE |
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