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

Dadda, Adilio da S; Rodrigues-Junior, Valnês S; Carreño, Fernando; Petersen, Guilherme O; Pinto, Antônio F M; Dalberto, Pedro F; Sperotto, Nathalia D M; Pissinate, Kenia; Bizarro, Cristiano V; Machado, Pablo; Campos, Maria M; Costa, Teresa Dalla; Santos, Diógenes S; Basso, Luiz A.
Eur J Pharm Sci; 111: 393-398, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29037995
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 (t1/2) (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.
Selo DaSilva