Influence of the binding of reduced NAMI-A to human serum albumin on the pharmacokinetics and biological activity
Rattachement africain : cz, us, it. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
NAMI-A is a ruthenium-based drug endowed with the unique property of selectively targeting solid tumour metastases. Although two clinical studies had already been completed, limited information exists on the behavior of NAMI-A after injection into the bloodstream. PK data in humans informs us of a rather low free drug concentration, of a relatively high half-life time of elimination and of a linear relationship between the administered dose and the corresponding AUC for up to toxic doses. In the present study, we examined the chemical kinetics of albumin binding with or without the presence of reducing agents, and we evaluated how these chemical aspects might influence the in vivo PK and the in vitro ability of NAMI-A to inhibit cell migration, which is a bona fide, rapid and easy way to suggest anti-metastatic properties. The experimental data support the binding of NAMI-A to serum albumin. The reaction is facilitated when the drug is in its reduced form and, in agreement with already reported data, the adduct formed with albumin maintains the biological activity of the ruthenium drug. The formation of the adduct is favored by low ratios of NAMI-A : HSA and by the reduction of the drug with ascorbic acid. The difference in in vivo PK and the faster binding to albumin of the reduced NAMI-A seem to suggest that the drug is not rapidly reduced immediately upon injection, even at low doses. Most probably, cell and protein binding prevail over the reduction of the drug. This observation supports the thesis that the reduction of the drug before injection must be considered relevant for the pharmacological activity of NAMI-A against tumour metastases.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Influence of the binding of reduced NAMI-A to human serum albumin on the pharmacokinetics and biological activity
- Date Crossref
- 01/01/2015
- Éditeur
- Royal Society of Chemistry (RSC)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Czech Academy of Sciences pays non établi dans la noticeOrganisme public
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Palacký University Olomouc pays non établi dans la noticeUniversité ou école supérieure
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PLUS Foundation pays non établi dans la noticeOrganisation à but non lucratif
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University of Trieste Department of Life Sciences pays non établi dans la noticeUniversité ou école supérieure
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Academy of Sciences of the Czech Republic pays non établi dans la noticeStructure de recherche
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CZ-61265 Brno pays non établi dans la noticeInstitution
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Department of Biophysics pays non établi dans la noticeInstitution
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Institute of Biophysics pays non établi dans la noticeStructure de recherche
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Faculty of Science Department of Biophysics pays non établi dans la noticeUniversité ou école supérieure
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34127-Trieste pays non établi dans la noticeInstitution
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Callerio Foundation Onlus pays non établi dans la noticeOrganisation à but non lucratif
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Italy pays non établi dans la noticeInstitution
Czech Academy of Sciences, Palacký University Olomouc et PLUS Foundation, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.