11 / 17
Page 57
allied
academies
J Clin Exp Tox 2017 | Volume 1 | Issue 2
Toxicology and Pharmacology
November 01-02, 2017 | Toronto, Canada
International Conference on
T
he 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 28
th
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 29
th
and 70
th
day of protocol. Drug interaction was
assessed by evaluating the plasma drug concentration
using HPLC-UV and also determined 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 70
th
day of
protocol. Molecular modelling 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 CYP2C9 and
GLIM has strong hydrogen bond with polar contacts 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.
e:
shloksk@gmail.comMolecular modeling- a tool for postulating the mechanism of drug interaction: glimepiride alters the
pharmacokinetics of sildenafil citrate in diabetic nephropathy animals
Alok Shiomurti Tripathi
1, 2
, Ajay Kumar Timiri
2
, Papiya Mitra Mazumder
2
, Anil Chandewar
3
1
Kannur Medical College, India
2
Birla Institute of Technology, India
3
P Wadhwani College of Pharmacy, India