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Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism"

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An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI). During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI. | McDonnell et al. BMC Psychiatry 2010 10 45 http www.biomedcentral.com 1471-244X 10 45 BMC Psychiatry RESEARCH ARTICLE Open Access Post-injection delirium sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection II investigations of mechanism David P McDonnell 1 Holland C Detke1 Richard F Bergstrom2 Prajakti Kothare1 Jason Johnson1 Mary Stickelmeyer1 Manuel V Sanchez-Felix1 Sebastian Sorsaburu1 and Malcolm I Mitchell1 Abstract Background Olanzapine long-acting injection LAI is a salt-based depot antipsychotic combining olanzapine and pamoic acid. The slow intramuscular dissolution of this practically insoluble salt produces an extended release of olanzapine lasting up to 4 weeks. However in a small number of injections 0.1 patients experienced symptoms suggestive of olanzapine overdose a phenomenon that has been termed post-injection delirium sedation syndrome PDSS . The authors conducted a series of parallel investigations into the possible reasons PDSS events occur. Methods Healthcare providers involved in the PDSS cases were queried for clinical information around the events. Plasma samples from patients experiencing PDSS were collected when possible 12 30 cases and olanzapine concentrations compared with the known pharmacokinetic profile for olanzapine LAI. Product batches and used vials from the PDSS cases were evaluated for compliance with established manufacturing standards and or possible user error. Because this depot formulation depends upon slow dissolution at the intramuscular injection site in-vitro experiments were conducted to assess solubility of olanzapine pamoate in various media. Results Injection administrators reported no unusual occurrences during the injection. No anomalies were found with the product batches or the remaining suspension in the used vials. Olanzapine concentrations during PDSS events were higher than the expected 5-73 ng mL range with concentrations exceeding 100 ng mL and in some cases .