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The aim of this prospective, randomized, double-blind, dual-center, placebo-controlled trial was to evaluate the safety, tolerability, and pharmacokinetics of a single intravenous infusion of CsA in patients with severe TBI. Fifty adult severe TBI patients were enrolled over a 22-month period. Within 12\u2009h of the injury patients received 5\u2009mg\/kg of CsA infused over 24\u2009h, or placebo. Blood urea nitrogen (BUN), creatinine, hemoglobin, platelets, white blood cell count (WBC), and a hepatic panel were monitored on admission, and at 12, 24, 36, and 48\u2009h, and on days 4 and 7. Potential adverse events (AEs) were also recorded. Neurological outcome was recorded at 3 and 6 months after injury. This study revealed only transient differences in BUN levels at 24 and 48\u2009h and for WBC counts at 24\u2009h between the CsA and placebo patients. These modest differences were not clinically significant in that they did not negatively impact on patient course. Both BUN and creatinine values, markers of renal function, remained within their normal limits over the entire monitoring period. There were no significant differences in other mean laboratory values, or in the incidence of AEs at any other measured time point. Also, no significant difference was demonstrated for neurological outcome. Based on these results, we report a good safety profile of CsA infusion when given at the chosen dose of 5\u2009mg\/kg, infused over 24\u2009h, during the early phase after severe head injury in humans, with the aim of neuroprotection.<\/jats:p>","DOI":"10.1089\/neu.2009.1012","type":"journal-article","created":{"date-parts":[[2009,7,21]],"date-time":"2009-07-21T08:31:58Z","timestamp":1248165118000},"page":"2195-2206","source":"Crossref","is-referenced-by-count":98,"title":["Safety and Tolerability of Cyclosporin A in Severe Traumatic Brain Injury Patients: Results from a Prospective Randomized Trial"],"prefix":"10.1177","volume":"26","author":[{"given":"Anna Teresa","family":"Mazzeo","sequence":"first","affiliation":[{"name":"University of Messina","place":["Italy"]}]},{"given":"Gretchen M.","family":"Brophy","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University"}]},{"given":"Charlotte B.","family":"Gilman","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University"}]},{"given":"\u00d3scar Lu\u00eds","family":"Alves","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universitade do Porto","place":["Portugal"]}]},{"given":"Jaime R.","family":"Robles","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University"}]},{"given":"Ronald L.","family":"Hayes","sequence":"additional","affiliation":[{"name":"University of Florida"}]},{"given":"John T.","family":"Povlishock","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University"}]},{"given":"M. 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