Influence of the binding of reduced NAMI-A to human serum albumin on the pharmacokinetics and biological activity

0442387 - BFÚ 2015 RIV GB eng J - Článek v odborném periodiku
Novohradský, Vojtěch - Bergamo, A. - Cocchietto, M. - Zajac, J. - Brabec, Viktor - Mestroni, G. - Sava, G.
Influence of the binding of reduced NAMI-A to human serum albumin on the pharmacokinetics and biological activity.
Dalton Transactions. Roč. 44, č. 4 (2015), s. 1905-1913. ISSN 1477-9226. E-ISSN 1477-9234
Institucionální podpora: RVO:68081707
Klíčová slova: CELL-CYCLE ARREST * RUTHENIUM COMPLEX * ANTICANCER AGENT
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 4.177, rok: 2015

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.
Trvalý link: http://hdl.handle.net/11104/0245230