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

Hirata, Kenshiro; Ikeda, Tokunori; Watanabe, Hiroshi; Maruyama, Toru; Tanaka, Motoko; Chuang, Victor Tuan Giam; Uchida, Yuji; Sakurama, Keiki; Nishi, Koji; Yamasaki, Keishi; Otagiri, Masaki

doi:10.3390/toxins13110811

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…For aripiprazole, the equivalent calculation – 180 ng/ml and 0.64% unbound (Hirata 2021) – yields 2.57 nM free drug from which, with a K d of 0.34 nM (Burris 2002), an occupancy of 88.3% is again calculated.…”

Section: Quantitative Examplesmentioning

confidence: 99%

Partial agonists of dopamine receptors: clinical effects and dopamine receptor interactions in combining aripiprazole with a full antagonist in treating psychosis

Cookson

Pimm²,

Reynolds³

2023

BJPsych advances

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SUMMARY Partial agonists of dopamine receptors are used in combination with full antagonists in treating psychosis, either to mitigate side-effects or in the hope of increasing effectiveness. We examine how combinations may affect the occupancy of D2/D3 dopamine receptors and explore how these can explain the outcomes in the light of the dopamine hypothesis of psychosis. The combinations considered here are from published studies combining aripiprazole with amisulpride, with risperidone in people with hyperprolactinaemia and with olanzapine to mitigate weight gain. We discuss possible worsening of symptoms by the addition of a partial agonist or switching. We also examine the potentially adverse interaction with a full antagonist such as haloperidol given during a subsequent relapse to control severe agitation.

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Section: Quantitative Examplesmentioning

confidence: 99%

Partial agonists of dopamine receptors: clinical effects and dopamine receptor interactions in combining aripiprazole with a full antagonist in treating psychosis

Cookson

Pimm²,

Reynolds³

2023

BJPsych advances

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“…The binding of aripiprazole in the cases of renal failure was reduced significantly, compared with the same values for healthy adults. An association was found between the ARP binding rate and the concentration of toxins, including IS and PCS [ 62 ].…”

Section: Interaction Between Uremic Toxins and Albuminmentioning

confidence: 99%

The Interplay between Uremic Toxins and Albumin, Membrane Transporters and Drug Interaction

Cunha

Azevedo

Falconi

et al. 2022

Toxins

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Uremic toxins are a heterogeneous group of molecules that accumulate in the body due to the progression of chronic kidney disease (CKD). These toxins are associated with kidney dysfunction and the development of comorbidities in patients with CKD, being only partially eliminated by dialysis therapies. Importantly, drugs used in clinical treatments may affect the levels of uremic toxins, their tissue disposition, and even their elimination through the interaction of both with proteins such as albumin and cell membrane transporters. In this context, protein-bound uremic toxins (PBUTs) are highlighted for their high affinity for albumin, the most abundant serum protein with multiple binding sites and an ability to interact with drugs. Membrane transporters mediate the cellular influx and efflux of various uremic toxins, which may also compete with drugs as substrates, and both may alter transporter activity or expression. Therefore, this review explores the interaction mechanisms between uremic toxins and albumin, as well as membrane transporters, considering their potential relationship with drugs used in clinical practice.

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“…We recently studied the binding properties of ARP derivatives to plasma proteins as part of a preliminary pharmacokinetic evaluation of these molecules. ARP binds to human serum albumin (HSA) and the α 1 -acid glycoprotein. − ARP binds more strongly to HSA than the other ARP derivatives, and the binding affinity of ARP to HSA (5.94 × 10 6 M –1 ) is more than 50 times higher than that of deschloro-ARP (0.10 × 10 6 M –1 ) . We determined the crystal structure of HSA complexed with ARP, and the results indicated that the binding position of ARP overlaps with the fatty acid binding sites 3 and 4 in HSA .…”

Section: Introductionmentioning

confidence: 99%

Chlorine Atoms of an Aripiprazole Molecule Control the Geometry and Motion of Aripiprazole and Deschloro-aripiprazole in Subdomain IIIA of Human Serum Albumin

et al. 2022

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Aripiprazole (ARP), an antipsychotic drug, binds more strongly to human serum albumin (HSA) than the other ARP derivatives. In addition, the signs for the extrinsic Cotton effects for HSA complexed with ARP or deschloro-ARP are reversed. In this study, we report on a structural–chemical approach using circular dichroism (CD) spectroscopic analysis, X-ray crystallographic analysis, and molecular dynamics simulations. The objective was to examine the relationship between the induced CD spectra and the structural features of the HSA complexes with ARP or deschloro-ARP. The intensity of the induced CD spectra of the HSA complexes with ARP or deschloro-ARP was reduced with increasing temperature. We determined the crystal structure of the HSA complexed with deschloro-ARP in this study and compared it to HSA complexed with ARP that we reported previously. The comparison of these structures revealed that both ARP and deschloro-ARP were bound at the site II pocket in HSA and that the orientation of the molecules was nearly identical. Molecular dynamics simulations indicated that the molecular motions of ARP and deschloro-ARP within the site II pocket were different from one another and the proportion of stacking interaction formations of Tyr411 with the dihydroquinoline rings of ARP and deschloro-ARP was also different. These findings indicate that the induced CD spectra are related to the molecular motions and dynamic interactions of ARP and deschloro-ARP in HSA and may help to understand the molecular recognition and motion that occurs within the binding site for the other HSA ligands more clearly.

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

Cited by 4 publications

References 15 publications

Partial agonists of dopamine receptors: clinical effects and dopamine receptor interactions in combining aripiprazole with a full antagonist in treating psychosis

Partial agonists of dopamine receptors: clinical effects and dopamine receptor interactions in combining aripiprazole with a full antagonist in treating psychosis

The Interplay between Uremic Toxins and Albumin, Membrane Transporters and Drug Interaction

Chlorine Atoms of an Aripiprazole Molecule Control the Geometry and Motion of Aripiprazole and Deschloro-aripiprazole in Subdomain IIIA of Human Serum Albumin

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