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The aim of the present study was to determine the effect of sildenafil on dopamine, 5-hydroxyindol acetic acid (5-HIAA) and selected biomarkers of oxidative stress in the brain of hypoglycemic rats. The animals were treated intraperitoneally as follows: group 1 (control), saline solution; group 2, insulin (10 U per rat or 50 U kg−1); group 3, insulin + single dose of sildenafil (50 U kg−1+ 50 mg kg–1); group 4, insulin + three doses of sildenafil every 24 hours (50 U kg−1+ 50 mg kg−1). In groups 2, 3 and 4, insulin was administered every 24 hours for 10 days. Blood glucose was measured after the last treatment. On the last day of the treatment, the animals´ brains were extracted to measure the levels of oxidative stress markers [H2O2, Ca2+,Mg2+-ATPase, glutathione and lipid peroxidation (TBARS)], dopamine and 5-HIAA in the cortex, striatum and cerebellum/medulla oblongata by validated methods. The results suggest that administration of insulin in combination with sildenafil induces hypoglycemia and hypotension, enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines. Administration of insulin and sildenafil promotes biometabolic responses in glucose control, namely, it induces hypoglycemia and hypotension. It also enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines.

Background Food can affect the bioavailability of various drugs, and the consistency of food may also affect the bioavailability of drugs when they have to be given simultaneously. Alterations of ranitidine bioavailability due to food consistency have not been well documented.Objective To evaluate the effect of food consistency on the pharmacokinetics of ranitidine.Methods The study included 20 healthy volunteers. In the first phase, volunteers received oral ranitidine 300 mg after a meal of solid consistency (SC). Two weeks later (washout period), subjects took the medication after ingesting food of liquid consistency (LC); blood samples were drawn for both groups at the same intervals and were analyzed using HPLC.Results The AUC was nearly 30% greater with LC than with SC, maximum concentration was 665.81 ± 192.21 (SC) versus 1177.30 ± 588.19 ng/mL (LC). Mean ± SD volume of distribution was 5.93 ± 1.69 (SC) versus 3.76 ± 0.61 L/kg (LC). These differences were statistically significant (p < 0.05).Conclusions It is evident that there are differences in drug availability due to the ingestion of foods with different consistency. It is possible that altered bioavailability of ranitidine affects its efficacy as an inhibitor of gastric secretion.