TY - JOUR
T1 - Enhancing the oral bioavailability of asenapine maleate with bio-enhancer
T2 - An in-silico assisted in-vivo pharmacokinetic study
AU - Suresh, Akhil
AU - Narayan, Reema
AU - Tummala, Hari Prabhath
AU - Matcha, Saikumar
AU - Mallayasamy, Surulivelrajan
AU - Nayak, Yogendra
AU - Puralae Channabasavaiah, Jagadish
AU - Nayak, Usha Y.
N1 - Funding Information:
Science and Engineering Research Board, Dept. of Science and Technology, New Delhi, India (Ref. No. EMR/2016/007006).Authors express their gratitude to Apotex Research Pvt. Ltd. Bommasandra Industrial Area, Bangalore, India for providing gift sample of Asenapine maleate. We sincerely thank Science and Engineering Research Board, Dept. of Science and Technology, New Delhi, India for supporting this work by providing the grant for the infrastructure facility to carry out computational studies. Authors are thankful to Manipal Academy of Higher Education (MAHE), Manipal, India, for providing Dr TMA Pai Fellowship to Akhil Suresh.
Funding Information:
Authors express their gratitude to Apotex Research Pvt. Ltd., Bommasandra Industrial Area, Bangalore, India for providing gift sample of Asenapine maleate. We sincerely thank Science and Engineering Research Board , Dept. of Science and Technology, New Delhi, India for supporting this work by providing the grant for the infrastructure facility to carry out computational studies. Authors are thankful to Manipal Academy of Higher Education (MAHE), Manipal, India, for providing Dr TMA Pai Fellowship to Akhil Suresh.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jddst.2022.103215
DO - 10.1016/j.jddst.2022.103215
M3 - Article
AN - SCOPUS:85125869182
SN - 1773-2247
VL - 70
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
M1 - 103215
ER -