Sildenafil citrate (SIL) is used in the treatment of erectile dysfunction and other chronic disorders. For the pharmacokinetic investigation of SIL we developed a simple and sensitive method for the estimation of 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 SIL was found to be 4.0 min having a separation time less than 5 min. The developed method was validated for accuracy, precision, linearity and recovery. Linearity studies were found to be acceptable over the range of 0.1-6 μg/ml. The method was successfully applied for the analysis of rat plasma sample for the application in pharmacokinetic study, drug interaction, bioavailability and bioequivalence.

AimThe present investigates deals with the change in the pharmacokinetic of Sildenafil citrate (SIL) in disease condition like diabetic nephropathy (DN).MethodDiabetes was induced in rats by administering Streptozotocin i.e. STZ (60 mg/kg, IP) saline solution. Assessment of diabetes was done by GOD-POD method and conformation of DN was done by assessing the level of Creatinine, Blood Urea Nitrogen (BUN) and Albuminurea. After the conformation of DN single dose of drug SIL (2.5 mg/kg, p.o.) were given orally and Pharmacokinetic Parameters like [AUC o-t (ug.h/ml), AUC 0-∞, Cmax, Tmax, Kel, Clast] were estimated in the plasma by the help of HPLC-UV.ResultThere was significant increase (p < 0.01) in the Pharmacokinetic parameters of SIL in DN rat (AUC0-t, AUC0-∞, Cmax, Tmax and T1/2) compare to normal control rat and significant increase Kel in the DN rat compare to control rat.ConclusionThe study concluded that there was significant (p < 0.01) increase in the bioavailability of SIL in DN.

The present study concludes that SIL improves the renal function by decreasing the triglyceride level and improving the podocyte count in DN animals.

Present study evaluate wound healing activity of ethanolic extract of stem bark of Pongamia pinnata (PP). Evaluation of wound healing activity, 2 wound models were used I. e., incision and excision wounds were perform in this study on Albino wistar rats (150-200 g). The rats were been treated with 10% and 5% ointment base formulation at dose 15 µl/wound topically. The parameters studied were breaking strength in case of incision wounds, epithelization period and wound area in case of excision wound. The ethanolic extract treated group showed a significant (P < 0.01) reduction in the wound breaking strength in incision type of wound model and significant increase in epithelization period and reduction in percentage of wound area in excision type of wound model as compared to control group. Extract treated groups showed significant (P < 0.01) improvement in all the wound healing parameters of incision and excision wound models as compared to control. This study justify the traditional use of ethanolic extract of Pongamia pinnata stem bark shows wound healing property.

Aim:The aim of this study was to analyze the ethyl acetate extract of Nerium indicum (NIE) flower for its antioxidant effect in anxious Sprague–Dawley rats.Materials and Methods:Animals were divided into six groups (n = 6) and treated with 200 mg/kg and 400 mg/kg p.o. of NIE for 21 days to assess its preventive and curative effects. Anxiety was induced by isolating animals socially for 21 days. Elevated plus maze (EPM) and light and dark model were used for measuring anxiety in animals. Oxidative stress parameters such as lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in blood and brain tissue homogenate were monitored after 21 days of social isolation in animals.Results:Rats were treated with NIE 200 mg/kg and 400 mg/kg p.o. Both the treatments showed a significant (P < 0.001) increase in the number of open arm entries and time spent in open arm in EPM when compared with the negative control. Results also demonstrated that there was a significant (P < 0.001) increase in the number of lightbox entries and time spent in light box in light and dark model when compared with negative control. There was a significant (P < 0.001) improvement in endogenous anti-oxidants such as SOD, CAT, reduced GSH, and decreased levels of LPO in blood and brain tissue when compared with the negative control.Conclusion:The present study suggests the role of NIE in the treatment of anxiety, possibly by modulating the oxidative stress.

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.

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.

The present study investigate the drug interaction of Glimepiride (GLIM) with Sildenafil Citrate (SIL) in Diabetic Nephropathy (DN) rats. Diabetes was induced in rats by administering Streptozotacin i. e. STZ (60 mg/kg). In present investigation GLIM (0.5 mg/kg, P.O.) and SIL (2.5 mg/kg, P.O.) were given for 6 weeks after the confirmation of DN. Pharmacodynamic and kinetic parameters were estimated after 1(st) dose and at the end of 6(th) week of drug administration. There was significant (p<0.001) increase in the bioavailability of GLIM in the presence of SIL in DN after the 1(st) dose of administration of the drug as compared to GLIM treated rat, whereas at the end of 6(th) week of drug administration, there were significant (p<0.0001) decrease in the bioavailability of GLIM+SIL treated DN rats compared to GLIM treated rats. There was significant (P<0.01) reduction of blood glucose level in GLIM+SIL treated group as compare to only GLIM treated group on 1(st) dose of drug administration but after continuous treatment for next 6 weeks, GLIM treated group showed significant hypoglycemia which was found to be reduced in GLIM+SIL treated group significantly. The present study concluded that GLIM+SIL treatment reduces the hypoglycemic condition which was there for GLIM treated DN rat.