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The Binding of Aripiprazole to Plasma Proteins in Chronic Renal Failure Patients

Authors :
Kenshiro Hirata
Tokunori Ikeda
Hiroshi Watanabe
Toru Maruyama
Motoko Tanaka
Victor Tuan Giam Chuang
Yuji Uchida
Keiki Sakurama
Koji Nishi
Keishi Yamasaki
Masaki Otagiri
Source :
Toxins, Vol 13, Iss 11, p 811 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

The binding of drugs to plasma protein is frequently altered in certain types of renal diseases. We recently reported on the effects of oxidation and uremic toxins on the binding of aripiprazole (ARP) to human serum albumin. In our continuing investigations, we examined the binding of ARP to plasma pooled from patients with chronic renal dysfunction. We examined the issue of the molecular basis for which factors affect the changes in drug binding that accompany renal failure. The study was based on the statistical relationships between ARP albumin binding and biochemical parameters such as the concentrations of oxidized albumin and uremic toxins. The binding of ARP to plasma from chronic renal patients was significantly lower than healthy volunteers. A rational relationship between the ARP binding rate and the concentration of toxins, including indoxyl sulphate (IS) and p-cresyl sulphate (PCS), was found, particularly for IS. Moreover, multiple regression analyses that involved taking other parameters such as PCS or oxidized albumin ratio to IS into account supports the above hypothesis. In conclusion, the limited data reported in this present study indicates that monitoring IS in the blood is a very important determinant in the dosage plan for the administration of site II drugs such as ARP, if the efficacy of the drug in renal disease is to be considered.

Details

Language :
English
ISSN :
20726651
Volume :
13
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Toxins
Publication Type :
Academic Journal
Accession number :
edsdoj.5521bd7ff6104aa1a466933dd37f6b68
Document Type :
article
Full Text :
https://doi.org/10.3390/toxins13110811