RESUMO
The aim of our study was to enhance the bioavailability of ranolazine by using herbal-bioenhancer quercetin in rats and to study the role of P-glycoprotein (P-gp) in vitro models. In single dose study (SDS), rats were divided into four groups, Group I was treated with 0.5% sodium carboxy methyl cellulose (SCMC), Group II was treated with ranolazine (14 mg/kg), Group III was treated with quercetin (20 mg/kg) and Group IV was treated with both ranolazine and quercetin. The blood samples were collected at 0.5, 1, 2, 3, 4, 6, 8 and 12 h, and the concentration of ranolazine in the plasma was estimated by reverse phase high performance liquid chromatography (RP-HPLC) method. In multiple dose study (MDS), rats were treated with same drugs for 7 days. On 8th day, the concentration of ranolazine in plasma was estimated. In vitro study performed on the rat and chick intestinal sacs to study the intestinal transport of ranolazine in the presence and absence of quercetin and verapamil (P-gp-inhibitor). Quercetin increased the peak concentration (Cmax) of ranolazine from 254 ± 8.45 to 324 ± 10.21 and 331 ± 9.65 ng/mL in SDS and MDS, respectively. Quercetin also increased area under the curve (AUC) of ranolazine from 1565.12 ± 52.24 to 2016.98 ± 142.65 and 2070.85 ± 271.60 ng/mL/h in SDS and MDS, respectively. The transport of ranolazine from mucosal side to serosal side was increased in presence of quercetin. Quercetin is an inhibitor of CYP3A4 and P-gp. So it increased the AUC and Cmax of ranolazine.
Assuntos
Acetanilidas/sangue , Antioxidantes/metabolismo , Piperazinas/sangue , Quercetina/sangue , Bloqueadores dos Canais de Sódio/sangue , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Acetanilidas/farmacologia , Animais , Antioxidantes/farmacologia , Galinhas , Interações Medicamentosas/fisiologia , Inibidores Enzimáticos/sangue , Inibidores Enzimáticos/farmacologia , Absorção Intestinal/efeitos dos fármacos , Absorção Intestinal/fisiologia , Masculino , Técnicas de Cultura de Órgãos , Piperazinas/farmacologia , Quercetina/farmacologia , Ranolazina , Ratos , Ratos Wistar , Bloqueadores dos Canais de Sódio/farmacologiaAssuntos
Aldeído Redutase/antagonistas & inibidores , Aspergillus niger/metabolismo , Inibidores Enzimáticos/química , Naftoquinonas/química , Aspergillus niger/química , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Fermentação , Estrutura Molecular , Peso Molecular , Naftoquinonas/isolamento & purificação , Naftoquinonas/metabolismo , Naftoquinonas/farmacologia , Ressonância Magnética Nuclear Biomolecular , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
An enzyme inhibitor, nigerloxin, with inhibition against soy bean lipoxygenase-I (LOX-1), rat lens aldose reductase (RLAR) as well as free radical scavenging activity was isolated from the fermented wheat bran using Aspergillus niger CFR-W-105. Its chemical structure was identified as 2-amido-3-hydroxy-6-methoxy-5-methyl-4-(prop-1'-enyl) benzoic acid by NMR and GCEIMS data. The IC50 values against LOX-1 and RLAR were found to be 79 microM and 69 microM and ED50 against 1,1-diphenyl-2-picrylhydrazyl (DPPH) was 66 microM.