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Pharmacokinetics and hematotoxicity of a novel copper-based anticancer agent: casiopeina III-Ea, after a single intravenous dose in rats

Citation

Vertiz, G and Garcia-Ortuno, LE and Bernal, JP and Bravo-Gomez, ME and Lounejeva, E and Huerta, A and Ruiz-Azuara, L, Pharmacokinetics and hematotoxicity of a novel copper-based anticancer agent: casiopeina III-Ea, after a single intravenous dose in rats, Fundamental and Clinical Pharmacology, 28, (1) pp. 78-87. ISSN 0767-3981 (2014) [Refereed Article]

Copyright Statement

Copyright 2014 The Authors Fundamental and Clinical Pharmacology

DOI: doi:10.1111/j.1472-8206.2012.01075.x

Abstract

Casiopeina III-Ea is a mixed chelate copper (II) complex that has shown cytotoxic and antitumor activity in vitro and in vivo. The aim of this study was to investigate the pharmacokinetics of total copper derived from casiopeina III-Ea administered by intravenous bolus injection to Wistar rats. Other objective was to evaluate the hematotoxicity produced by this compound in those animals. Wistar rats received a single intravenous dose of 4 mg/kg of casiopeina III-Ea. Blood samples were taken and pharmacokinetics evaluated. Furthermore, erythrocyte copper levels were determined to identify a potential target and Zn levels were analyzed to determine a possible change. For the evaluation of hematotoxicity, both blood and urine samples were collected for hematological and biochemical analyses; moreover, Fe determination was performed. Blood copper and zinc levels, red blood cell copper levels as well as copper, zinc, and iron amounts excreted into urine were analyzed by ICP-MS. The blood concentration–time profile of copper derived from casiopeina III-Ea was fitted to a two-compartment model with a zero-order input. Cumulative amounts of Cu, Zn, and Fe excreted into rat urine after administration of casiopeina III-Ea were different with respect to control. Hematological and biochemical data indicated a hemolytic toxicity. Pharmacokinetic analysis of total copper derived from casiopeina III-Ea provided a general knowledge about distribution and elimination process of this compound. Additionally, the systemic exposure of the copper derived from casiopeina III-Ea accounts for the hematotoxicity of this complex at test dose.

Item Details

Item Type:Refereed Article
Keywords:casiopeinas, copper, hematotoxicity, mixed chelate, pharmacokinetics
Research Division:Earth Sciences
Research Group:Geochemistry
Research Field:Inorganic Geochemistry
Objective Division:Manufacturing
Objective Group:Human Pharmaceutical Products
Objective Field:Human Pharmaceutical Treatments (e.g. Antibiotics)
Author:Lounejeva, E (Ms Elena Lounejeva Baturina)
ID Code:98508
Year Published:2014
Web of Science® Times Cited:11
Deposited By:Centre for Ore Deposit Research - CODES CoE
Deposited On:2015-02-18
Last Modified:2017-11-06
Downloads:0

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