The Binding of Aripiprazole to Plasma Proteins in Chronic Renal Failure Patients
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...
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2021
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oai:doaj.org-article:5521bd7ff6104aa1a466933dd37f6b682021-11-25T19:09:01ZThe Binding of Aripiprazole to Plasma Proteins in Chronic Renal Failure Patients10.3390/toxins131108112072-6651https://doaj.org/article/5521bd7ff6104aa1a466933dd37f6b682021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6651/13/11/811https://doaj.org/toc/2072-6651The 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.Kenshiro HirataTokunori IkedaHiroshi WatanabeToru MaruyamaMotoko TanakaVictor Tuan Giam ChuangYuji UchidaKeiki SakuramaKoji NishiKeishi YamasakiMasaki OtagiriMDPI AGarticleuremic toxinsindoxyl sulphaterenal diseaseprotein bindingaripiprazoleMedicineRENToxins, Vol 13, Iss 811, p 811 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
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| topic |
uremic toxins indoxyl sulphate renal disease protein binding aripiprazole Medicine R |
| spellingShingle |
uremic toxins indoxyl sulphate renal disease protein binding aripiprazole Medicine R Kenshiro Hirata Tokunori Ikeda Hiroshi Watanabe Toru Maruyama Motoko Tanaka Victor Tuan Giam Chuang Yuji Uchida Keiki Sakurama Koji Nishi Keishi Yamasaki Masaki Otagiri The Binding of Aripiprazole to Plasma Proteins in Chronic Renal Failure Patients |
| description |
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. |
| format |
article |
| author |
Kenshiro Hirata Tokunori Ikeda Hiroshi Watanabe Toru Maruyama Motoko Tanaka Victor Tuan Giam Chuang Yuji Uchida Keiki Sakurama Koji Nishi Keishi Yamasaki Masaki Otagiri |
| author_facet |
Kenshiro Hirata Tokunori Ikeda Hiroshi Watanabe Toru Maruyama Motoko Tanaka Victor Tuan Giam Chuang Yuji Uchida Keiki Sakurama Koji Nishi Keishi Yamasaki Masaki Otagiri |
| author_sort |
Kenshiro Hirata |
| title |
The Binding of Aripiprazole to Plasma Proteins in Chronic Renal Failure Patients |
| title_short |
The Binding of Aripiprazole to Plasma Proteins in Chronic Renal Failure Patients |
| title_full |
The Binding of Aripiprazole to Plasma Proteins in Chronic Renal Failure Patients |
| title_fullStr |
The Binding of Aripiprazole to Plasma Proteins in Chronic Renal Failure Patients |
| title_full_unstemmed |
The Binding of Aripiprazole to Plasma Proteins in Chronic Renal Failure Patients |
| title_sort |
binding of aripiprazole to plasma proteins in chronic renal failure patients |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/5521bd7ff6104aa1a466933dd37f6b68 |
| work_keys_str_mv |
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