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dc.contributor.authorBanis, G.E.
dc.contributor.authorWinkler, T.
dc.contributor.authorBarton, P.
dc.date.accessioned2019-07-15T16:12:13Z
dc.date.available2019-07-15T16:12:13Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85028552604&doi=10.3390%2fph10030069&partnerID=40&md5=17ff1d8b889fe50063f703f46a3190b4
dc.identifier.urihttp://hdl.handle.net/10713/9953
dc.description.abstractClozapine (CLZ), a dibenzodiazepine, is demonstrated as the optimal antipsychotic for patients suffering from treatment-resistant schizophrenia. Like many other drugs, understanding the concentration of CLZ in a patient’s blood is critical for managing the patients’ symptoms, side effects, and overall treatment efficacy. To that end, various electrochemical techniques have been adapted due to their capabilities in concentration-dependent sensing. An open question associated with electrochemical CLZ monitoring is whether drug–protein complexes (i.e., CLZ bound to native blood proteins, such as serum albumin (SA) or alpha-1 acid-glycoprotein (AAG)) contribute to electrochemical redox signals. Here, we investigate CLZ-sensing performance using fundamental electrochemical methods with respect to the impact of protein binding. Specifically, we test the activity of bound and free fractions of a mixture of CLZ and either bovine SA or human AAG. Results suggest that bound complexes do not significantly contribute to the electrochemical signal for mixtures of CLZ with AAG or SA. Moreover, the fraction of CLZ bound to protein is relatively constant at 31% (AAG) and 73% (SA) in isolation with varying concentrations of CLZ. Thus, electrochemical sensing can enable direct monitoring of only the unbound CLZ, previously only accessible via equilibrium dialysis. The methods utilized in this work offer potential as a blueprint in developing electrochemical sensors for application to other redox-active medications with high protein binding more generally. This demonstrates that electrochemical sensing can be a new tool in accessing information not easily available previously, useful toward optimizing treatment regimens. Copyright 2017 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.description.sponsorshipResearch reported in this publication was supported by the National Institute of Mental Health under award number 1R56MH105571, as well as the National Science Foundation Graduate Research Fellowship Program Grant No. DGE00750616.en_US
dc.description.urihttps://www.doi.org/10.3390/ph10030069en_US
dc.language.isoen_USen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofPharmaceuticals
dc.subjectAlbuminen_US
dc.subjectAlpha-1 acid-glycoproteinen_US
dc.subjectClozapineen_US
dc.subjectElectrochemistryen_US
dc.subjectUltrafiltrationen_US
dc.titleThe binding effect of proteins on medications and its impact on electrochemical sensing: Antipsychotic clozapine as a case studyen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/ph10030069


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