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Preclinical pharmacokinetic profiling of IQG-607, a potential oral metallodrug to treat tuberculosis. | LitMetric

Preclinical pharmacokinetic profiling of IQG-607, a potential oral metallodrug to treat tuberculosis.

Eur J Pharm Sci

Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Av. Ipiranga 6681 - Prédio 92A Tecnopuc, 90619-900 Porto Alegre, RS, Brazil; Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6681 - Prédio 92A Tecnopuc, 90619-900 Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, Brazil; Programa de Pós-Graduação em Medicina e Ciências da Saúde, PUCRS, Porto Alegre, Brazil. Electronic address:

Published: January 2018

AI Article Synopsis

Article Abstract

IQG-607 is an analog of isoniazid with anti-tuberculosis activity. This work describes the development and validation of an HPLC method to quantify pentacyano(isoniazid)ferrate(II) compound (IQG-607) and the pharmacokinetic studies of this compound in mice. The method showed linearity in the 0.5-50μg/mL concentration range (r=0.9992). Intra- and inter-day precision was <5%, and the recovery ranged from 92.07 to 107.68%. IQG-607 was stable in plasma for at least 30days at -80°C and, after plasma processing, for 4h in the auto-sampler maintained on ice (recovery >85%). The applicability of the method for pharmacokinetic studies was determined after intravenous (i.v.) and oral (fasted and fed conditions) administration to mice. IQG-607 levels in plasma were quantified at time points for up to 2.5h. A short half-life (t) (1.14h), a high clearance (CL) (3.89L/h/kg), a moderate volume of distribution at steady state (Vdss) of 1.22L/kg, were observed after i.v. (50mg/kg) administration. Similar results were obtained for oral administration (250mg/kg) under fasted and fed conditions. The oral bioavailability (F), approximately 4%, was not altered by feeding. Plasma protein binding was 88.87±0.9%. The results described here provide novel insights into a pivotal criterion to warrant further efforts to be pursued towards attempts to translate this chemical compound into a chemotherapeutic agent to treat TB.

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http://dx.doi.org/10.1016/j.ejps.2017.10.020DOI Listing

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