toxicology-congress-2018-posters-accepted-abstracts

27 / 36

Page 95
conferenceseries.com
Volume 4 Toxicology: Open Access
ISSN: 2476-2067 Toxicology Congress 2018
March 12-14, 2018
March 12-14, 2018 Singapore
14th World Congress on
Toxicology and Pharmacology
Molecular modeling a tool for postulating the mechanism of drug interaction: Glimepiride alters the
pharmacokinetics of Sildenafil Citrate in diabetic nephropathy animals
Alok Shiomurti Tripathi1,2, Ajay Kumar Timiri2, Papiya Mitra Mazumder2 and Anil Chandewar3
1Kannur Medical College, India
2Birla Institute of Technology, India
3P Wadhwani College of Pharmacy, India
The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in
streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of
interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, IP) and
confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were
used for the drug interaction between GLIM (0.5 mg/kg, P.O.) and SIL (2.5 mg/kg, P.O.) after 29th and 70th day of protocol.
Drug interactions were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change
in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study
using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine
biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when
co administered with GLIM after 70th day of protocol. Molecular modeling study revealed few important interactions with
rat serum albumin and CYP2C9. GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin
compared to SIL, whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contact and hydrophobic interactions
than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the
management of DN animals and mechanism has been supported by molecular modeling studies.
Toxicol Open Access 2018, Volume 4
DOI: 10.4172/2476-2067-C1-006