Pre-clinical pharmacokinetics evaluation of an anticonvulsant candidate benzaldehyde semicarbazone free and included in beta-cyclodextrin.
The 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 beta-cyclodextrin (BS/beta-CD). Free BS and BS/beta-CD were administered to male Wistar rats as a 10mg/kg intravenous bolus dose. For the oral route, 50mg/kg and 100mg/kg doses of the free drug and 50mg/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 (10mg/kg) and oral (50mg/kg) administration, the V(d) (1.6+/-0.5 and 2.2+/-0.8L/kg, respectively) and the Cl(tot) (1.4+/-0.5 and 1.8+/-0.5L/hkg, respectively) determinated for the BS/beta-CD complex were higher than those obtained for the free drug, but the t(1/2) (0.8+/-0.1h) was similar (p<0.05). The oral bioavailability of the BS/beta-CD complex (approximately 37%) was approximately 2-fold of the free BS ( approximately 20%). The higher drug brain penetration (2.8) after BS/beta-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.
Kaiser
Moacir
M
Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Farmacêuticas, Av. Ipiranga, 2752 Porto Alegre, RS 90610-000, Brazil.
Azeredo
Francine Johansson
FJ
Uchôa
Flávia De Toni
Fde T
Beraldo
Heloísa de Oliveira
Hde O
Dalla Costa
Teresa
T
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012664:Semicarbazones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000927:Anticonvulsants; D012664:Semicarbazones; C512112:benzaldehyde semicarbazone; D047392:beta-Cyclodextrins; C031215:betadex