Produção Nacional
Revisado por pares
Pre-clinical pharmacokinetics evaluation of an anticonvulsant candidate benzaldehyde semicarbazone free and included in β-cyclodextrin
2010; Elsevier BV; Volume: 39; Issue: 5 Linguagem: Inglês
10.1016/j.ejps.2010.01.003
ISSN1879-0720
AutoresMoacir Kaiser, Francine Johansson Azeredo, Flávia De Toni Uchôa, Heloísa Beraldo, Teresa Dalla Costa,
Tópico(s)Drug Solubulity and Delivery Systems
ResumoThe study aimed to investigate the pharmacokinetics and tissue distribution of the benzaldehyde semicarbazone (BS) a potential antiepileptic drug, administered as a free drug or complexed β-cyclodextrin (BS/β-CD). Free BS and BS/β-CD were administered to male Wistar rats as a 10 mg/kg intravenous bolus dose. For the oral route, 50 mg/kg and 100 mg/kg doses of the free drug and 50 mg/kg of the complex were administrated and plasma concentrations were determinated by a validated HPLC-UV method. Individual profiles were evaluated by non-compartmental and compartmental analysis using Excel® and Scientist®, respectively. Free BS plasma protein binding was 34 ± 5%. A one-compartmental model adequately described all the plasma profiles for both formulations. After intravenous (10 mg/kg) and oral (50 mg/kg) administration, the Vd (1.6 ± 0.5 and 2.2 ± 0.8 L/kg, respectively) and the Cltot (1.4 ± 0.5 and 1.8 ± 0.5 L/h kg, respectively) determinated for the BS/β-CD complex were higher than those obtained for the free drug, but the t1/2 (0.8 ± 0.1 h) was similar (p < 0.05). The oral bioavailability of the BS/β-CD complex (∼37%) was approximately 2-fold of the free BS (∼20%). The higher drug brain penetration (2.8) after BS/β-CD dosing and the longer mean residence time in this organ, regardless of the administration route, reveals that the complex may be a potential drug carrier for the central nervous system delivery of BS.
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