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Cost of valsartan 40 mg ) or placebo for 48 hours before each study day, as well before each study medication dose (0, 8, and 16 mg/day) in order to determine the baseline levels of plasma concentrations the drug. subjects were then randomly assigned to receive the two dose levels on first test day (i.e., pretreatment on the before study onset or immediately in the period prior to study onset). During the week preceding each study day, subjects were monitored by the same investigator using an intravenous drug test to determine the plasma concentrations, which were confirmed by a microdialysis system (Deltatrac System, Inc, Tulsa, Oklahoma). Additionally, the blood and urine were analyzed for drug levels using an automated analyzer that analyzes creatinine and drug levels using gas chromatography/mass spectrometry in order to detect plasma levels <5 ng/mL, at times following the pharmacodynamic drug administration. The study was conducted blind to the subjects' demographics, clinical and laboratory status, treatment assignment; all the research personnel, including those who conducted the study and investigators, were double‐blinded Maxitrol gotas oftalmicas generico to the treatment assignment after receiving informed consent from the subjects after a medical history history, laboratory, blood and urine testing was completed. Dose titration. As the drug is metabolized, it expected that blood concentrations of the drug will gradually increase over the course of a day once the drug has accumulated to a concentration of 4–8 μM in plasma. To avoid side effects (e.g., central nervous system, cardiovascular effects, and gastrointestinal effects) when administering higher doses of valsartan in an unpredictable manner (> 2 μM), we used a dose-escalation schedule to test whether there is more than one route of administration by which the serum concentration could be significantly increased without having an additive effect [16]. Patients took a 2 mg dosage at 30 minutes prior to the first study day, and a 5 mg dosage at minutes prior to the second study day. A single dose of 0.05 mg valsartan per kilogram of body weight was administered on both study days for each subject. Valsartan was administered in single 1.5 mL intravenous doses administered hours apart. Blood samples for drug study administration were immediately available for valsartan analyses valsartan dura 160 mg kaufen after the initial study day. A urine sample (0.5 ml) was collected 1 hour after the administration of any valsartan dosage for determination of drug plasma concentration. Pharmacokinetic and pharmacodynamic effects. For plasma pharmacokinetics, valsartan was given in an intravenous infusion at a maximum rate of 8 gpm/min as the concentration was not monitored on the study day. infusion rate was progressively increased and maintained throughout the 96 hours of drug administration. The time to peak plasma drug concentration (Tmax) was 48 hours following the last dose. Tmax, as determined by the plasma valsartan concentration/area under (AUC) was 2.78 hours (95% CI: 2.50–2.96) postdose. AUC was calculated in the manner previously described by our group [17], where Tmax was determined by the product of plasma valsartan concentration and baseline concentration. AUC was calculated as follows: [AUC, in mg/L]/[log-time of AUC (hours)]. For pharmacodynamic studies, the AUC to peak plasma concentration for each drug were determined in the first 24 hours following last dose or, if not available within 24 hours, the last 8 hours following dose (i.e., within the cost of v