sildenafil-citrate and glimepiride

The present study evaluates the possible mechanism of sildenafil citrate (SIL) for the attenuation of renal failure in diabetic nephropathic (DN) animals.. Diabetic nephropathy was induced by a single dose of streptozotocin (STZ) (60 mg/kg, i.p.) and confirmed by assessing the blood and urine biochemical parameters on the 28th day of its induction. The selected DN animals were treated with glimepiride (0.5 mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) for a period of 6 weeks. Biochemical parameters in blood and urine were estimated after the 29th and 70th day of the protocol for the estimation of the effect of SIL.. There were significant alterations in the blood and urine biochemical parameters in STZ-treated groups which confirmed DN. There was a significant decrease in the triglyceride level in the SIL-only-treated group on the 70th day of the protocol. The histopathology study also suggested that SIL treatment results in the improvement in the podocyte count in DN animals.. The present study concludes that SIL improves the renal function by decreasing the triglyceride level and improving the podocyte count in DN animals.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Kidney Function Tests; Male; Phosphodiesterase 5 Inhibitors; Podocytes; Rats; Rats, Sprague-Dawley; Sildenafil Citrate; Streptozocin; Sulfonylurea Compounds; Triglycerides

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 (60 mg kg(-1), i.p.) and was confirmed by assessing blood and urine biochemical parameters 28 days after induction. Selected DN animals were used to explore the drug interaction between GLIM (0.5 mg kg(-1), p.o.) and SIL (2.5 mg kg(-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.

Topics: Animals; Blood Glucose; Cytochrome P-450 CYP2C9; Diabetic Nephropathies; Disease Models, Animal; Drug Interactions; Hypoglycemic Agents; Kidney Function Tests; Models, Molecular; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Phosphodiesterase 5 Inhibitors; Protein Conformation; Rats; Serum Albumin; Sildenafil Citrate; Structure-Activity Relationship; Sulfonylurea Compounds

A simple and sensitive method was developed for simultaneous estimation of Glimepiride (GLIM) and Sildenafil citrate (SIL) in rat Plasma by reverse phase high performance liquid chromatography (RP-HPLC). The drug samples were extracted by liquid-liquid extraction with 300 µl of acetonitrile and 5 ml of diethyl ether. Chromatographic separation was achieved on C18 column using methanol: water (85:15 v/v) as mobile phase at a flow rate of 1 ml/min and UV detection at 230 nm. The retention time of GLIM and SIL was found to be 2.5 and 4.0 min respectively with total run time of 7 min. The developed method was validated for accuracy, precision, linearity and recovery. The method was linear and found to be acceptable over the range of 100-12 000 ng/ml. The method was successfully applied for the analysis of rat plasma sample for application to pharmacokinetic.

Topics: Animals; Chromatography, High Pressure Liquid; Male; Piperazines; Purines; Rats; Rats, Sprague-Dawley; Sildenafil Citrate; Sulfones; Sulfonylurea Compounds