Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study.

BACKGROUND: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. METHODS: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. RESULTS: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. CONCLUSION: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

Neuro, cardio, and reno protective activities of rosuvastatin in streptozotocin-induced type 2 diabetic rats undergoing treatment with metformin and glimepiride.

Diabetes is associated with complications like neuropathy, nephropathy, cardiomyopathy, and retinopathy due to increased oxidative stress and serum lipids. In the present study, rosuvastatin, a HMG-CoA inhibitor, was investigated for its protective effect in neuropathy, nephropathy, and cardiomyopathy based on the lipid-lowering property along with its pleiotropic effects such as improved blood flow to the organ and antioxidant defense. Type 2 diabetes was induced in Wistar rats by single i.p. administration of streptozotocin (50 mg/kg). These diabetic rats were treated with daily doses of rosuvastatin (10 mg/kg) alone, metformin (120 mg/kg) and glimepiride (1 mg/kg) and rosuvastatin in combination with metformin (120 mg/kg) and glimepiride (1 mg/kg) for a period of 6 weeks. The biochemical parameters involved in neuropathy, renopathy, and cardiopathy were estimated. Treatment resulted in significant (P < 0.05) decrease in thiobarbituric acid reactive substances (TBARS) and increase in levels of glutathione peroxidise and catalase in brain and kidney homogenates. Significant (P < 0.05) increase in high-density lipoproteins and decrease in creatinine kinase, triglycerides, total serum cholesterol represents the cardioprotective action, whereas significant (P < 0.05) increase in the latency in the hotplate model shows the neuroprotective activity, and significant (P < 0.05) decrease in blood urea nitrogen, creatinine levels and increase in serum total protein levels suggested the renoprotective actions. The unique properties of rosuvastatin such as antioxidant defense and lipid-lowering nature might have resulted in cardio, neuro, and renoprotective activity in type 2 diabetic rats treated with metformin and glimepiride.