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Enalapril 20 gr x (500 mg) was administered at 2 or 4 h after i.v. administration of 0.25mg/kg b.i.d. oxazepam and 40 mg/kg i.v. of oxazepam (40 b.i.d. if co-administration required) in three groups. Patients were observed at baseline and 3, 6, 12 months in order to evaluate the pharmacokinetics of oxazepam (i.v.) during the active treatment and withdrawal. pharmacodynamics was also recorded at the same time points. study was approved by the local ethics committee. Twenty patients were included in the study. Results From the analysis by Cox proportional hazards model, the incidence of discontinuation increased significantly in the first 2 h, after which point no significant changes were observed in the remaining period. However, incidence of discontinuation was significantly greater after 3 h and remained significant longer than before 3 h after the initiation of treatment, in patients on oxazepam-controlled therapy (adjusted hazard ratio=4.8; p=0.02). The mean (and 95% CIs) cumulative incidence of discontinuation was 10.2±2.6 vs. 7.6±2.6 h (p=0.01), 12.8±2.2 9.8±2.8 (p=0.03), and 22.2±3.0 h (p=0.05) after the initiation of treatment with oxazepam. Conclusion It was found that pharmacokinetics of oxazepam in acute stroke patients are more affected by the length of time after drug initiation, and that the incidence of oxazepam discontinuation increases significantly after 2-2.5 h of treatment. Introduction The incidence of discontinuation drug therapy has been reported to be greater in patients who discontinued treatment (1–5). Studies have examined the pharmacokinetics and pharmacodynamics of oxazepam following either acute or recurrent stroke (6, 7). Although acute stroke is associated with a significant risk of death (1, 7, 8), a substantial minority of patients will experience acute stroke at some time before discharge from the hospital. Many of them (9) will have had severe head injury (HIC), and many of them will develop additional impairing neurological symptoms before discharge. Patients who have experienced acute stroke may not benefit from anticoagulation due to the high rate at which their blood is drawn (10). This high risk of discontinuation was observed in several studies and has been attributed to the use of drug in those patients for whom the need blood-thinning therapies is higher. In order to reduce this risk from oxazepam, oxazepam has been formulated using various mechanisms. In this study it was evaluated in the acute use and withdrawal to compare drug pharmacodynamics and pharmacokinetics of oxazepam in stroke patients taking either a propranolol (20 mg at 15 mg) or a combination of propranolol (20 mg plus 150 clopidogrel) and a combination of oxazepam (0.25 mg/kg, i.v.) Methods Study population The was approved by local ethics committee of the University Zurich, and written informed consents from all study participants received prior to baseline. Eligibility criteria included stroke patients with a known diagnosis of acute cerebral ischaemia by intracranial or periventricular haemorrhage contusion plus a positive drug screening. Two independent codefendants performed diagnostic criteria for the inclusion of stroke with acute ischaemia on a standardised stroke checklist at screening and 3 6 months after initiation of therapy. This criteria was also used in patients for whom a positive history or drug screen were not available. A detailed description of the protocol and methods used to detect stroke can be found in Appendix IV. Brief clinical information on all patients are presented in Table 1. Treatment group The patients (n=20) participating in this study were admitted to the Zurich General Hospital between January 2005 and July 2013 having acute ischaemic stroke of the brain at either 3 (n=6) or 6 (n=3) of the following levels: I, II and III. At screening patients were classified into treatment groups as follows: i) patients receiving propranolol/clopidogrel plus oxazepam (PR/CLOP): n=30; ii) patients Global canada pharmacy online receiving propranolol/clopidogrel plus propranolol (CLOP/CLOP): n=10; iii) patients receiving clopidogrel+propranolol (CL/Pro + CLOP): n=10; iv) patients receiving clopidogrel+propranolol + propranolol (CL/Pro CP2CLP.

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