Enhancing the oral bioavailability of asenapine maleate with bio-enhancer: An in-silico assisted in-vivo pharmacokinetic study

Abstract

The present work is aimed to address the oral bioavailability issue of asenapine maleate with the help of bio-enhancers. Molecular modeling platform by Maestro, Schrödinger was used to screen a list of bio-enhancer molecules. The bio-enhancer with the highest docking score and the best intermolecular interactions was selected for in-vivo pharmacokinetics studies. Of all the bio-enhancer molecules, quercetin showed the highest docking score (−10.6 on CYP1A2 and -9.34 on CYP3A4), induced fit docking score (−989.65 on CYP1A2 and -906.76 on CYP3A4) and greater association with proteins during molecular dynamics run. Animals were divided into five groups and orally administered with asenapine maleate and quercetin suspension at different dose and interval. The plasma was analyzed in high performance liquid chromatography, and various pharmacokinetic parameters were determined using Phoenix WinNonlin version 8.1. The presence of quercetin was found to significantly increase various pharmacokinetic parameters of asenapine maleate, and the groups administered with 25 mg/kg of quercetin showed better pharmacokinetic profile. A 2.5 folds increase in Cmax and 2.17 folds increase in AUC was observed in groups administered with quercetin. The increase in pharmacokinetic parameters could be attributed to the ability of the bio-enhancer to bind to the enzymes responsible for the metabolism of the drug, thereby prolonging the stay of drug in the body.