Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies
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| 024 | 7 | 0 | |a 10.1007/s00894-015-2823-x |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00894-015-2823-x | ||
| 245 | 0 | 0 | |a Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies |h [Elektronische Daten] |c [Alok Tripathi, Ajay Timiri, Papiya Mazumder, Anil Chandewar] |
| 520 | 3 | |a The present study evaluates possible drug interactions between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ)-induced diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction based on molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60mgkg−1, i.p.) and was confirmed by assessing blood and urine biochemical parameters 28days after induction. Selected DN animals were used to explore the drug interaction between GLIM (0.5mgkg−1, p.o.) and SIL (2.5mgkg−1, p.o.) on the 29th and 70th day of the protocol. Possible drug interaction was assessed by evaluating the plasma drug concentration using HPLC-UV and changes in biochemical parameters in blood and urine were also determined. The mechanism of the interaction was postulated from the results of a molecular modeling study using the Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in blood and urine biochemical parameters in STZ-treated groups. The concentration of SIL increased significantly (P < 0.001) in rat plasma when co-administered with GLIM on the 70th day of the protocol. Molecular modeling revealed important interactions with rat serum albumin and CYP2C9. GLIM has a strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL, whereas for CYP2C9, GLIM forms a stronger hydrogen bond than SIL with polar contacts and hydrophobic interactions. The present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals, and the mechanism is supported by molecular modeling studies. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2015 | ||
| 690 | 7 | |a Diabetic nephropathy |2 nationallicence | |
| 690 | 7 | |a Glimepiride |2 nationallicence | |
| 690 | 7 | |a Sildenafil citrate |2 nationallicence | |
| 690 | 7 | |a Pharmacokinetics |2 nationallicence | |
| 690 | 7 | |a Homology modeling |2 nationallicence | |
| 690 | 7 | |a Schrodinger |2 nationallicence | |
| 690 | 7 | |a Asn : Asparagine |2 nationallicence | |
| 690 | 7 | |a Arg : Arginine |2 nationallicence | |
| 690 | 7 | |a BLAST : Basic local alignment search tool |2 nationallicence | |
| 690 | 7 | |a cGMP : Cyclic guanosine mono phosphate |2 nationallicence | |
| 690 | 7 | |a CYP2C9 : Cytochrome P 450 2C9 |2 nationallicence | |
| 690 | 7 | |a CYP3b4 : Cytochrome P 450 3b4 |2 nationallicence | |
| 690 | 7 | |a Cys : Cysteine |2 nationallicence | |
| 690 | 7 | |a DN : Diabetic nephropathic |2 nationallicence | |
| 690 | 7 | |a HPLC : High pressure liquid chromatography |2 nationallicence | |
| 690 | 7 | |a GFR : Glomerular filtration rate |2 nationallicence | |
| 690 | 7 | |a GLIM : Glimepiride |2 nationallicence | |
| 690 | 7 | |a Gly : Glycine |2 nationallicence | |
| 690 | 7 | |a Leu : Leucine |2 nationallicence | |
| 690 | 7 | |a Lys : Lysine |2 nationallicence | |
| 690 | 7 | |a NO : Nitric oxide |2 nationallicence | |
| 690 | 7 | |a OPLS : Optimized potentials for liquid simulations |2 nationallicence | |
| 690 | 7 | |a Phe : Phenylalanine |2 nationallicence | |
| 690 | 7 | |a SIL : Sildenafil citrate |2 nationallicence | |
| 690 | 7 | |a STZ : Streptozotocin |2 nationallicence | |
| 690 | 7 | |a Tyr : Tyrosine |2 nationallicence | |
| 690 | 7 | |a Val : Valine |2 nationallicence | |
| 700 | 1 | |a Tripathi |D Alok |u Department of Pharmacology, P. Wadhwani College of Pharmacy, Dhamangaon Road, Girija Nagar, 445001, Yavatmal, MS, India |4 aut | |
| 700 | 1 | |a Timiri |D Ajay |u Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, 835215, Ranchi, Jharkhand, India |4 aut | |
| 700 | 1 | |a Mazumder |D Papiya |u Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, 835215, Ranchi, Jharkhand, India |4 aut | |
| 700 | 1 | |a Chandewar |D Anil |u Department of Pharmaceutical Chemistry, P. Wadhwani College of Pharmacy, 445001, Yavatmal, Maharashtra, India |4 aut | |
| 773 | 0 | |t Journal of Molecular Modeling |d Springer Berlin Heidelberg |g 21/10(2015-10-01), 1-10 |x 1610-2940 |q 21:10<1 |1 2015 |2 21 |o 894 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00894-015-2823-x |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00894-015-2823-x |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Tripathi |D Alok |u Department of Pharmacology, P. Wadhwani College of Pharmacy, Dhamangaon Road, Girija Nagar, 445001, Yavatmal, MS, India |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Timiri |D Ajay |u Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, 835215, Ranchi, Jharkhand, India |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Mazumder |D Papiya |u Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, 835215, Ranchi, Jharkhand, India |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Chandewar |D Anil |u Department of Pharmaceutical Chemistry, P. Wadhwani College of Pharmacy, 445001, Yavatmal, Maharashtra, India |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Molecular Modeling |d Springer Berlin Heidelberg |g 21/10(2015-10-01), 1-10 |x 1610-2940 |q 21:10<1 |1 2015 |2 21 |o 894 | ||