PMID- 19621985
OWN - NLM
STAT- MEDLINE
DCOM- 20100323
LR  - 20240409
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Print)
IS  - 0897-7151 (Linking)
VI  - 26
IP  - 12
DP  - 2009 Dec
TI  - Safety and tolerability of cyclosporin a in severe traumatic brain injury 
      patients: results from a prospective randomized trial.
PG  - 2195-206
LID - 10.1089/neu.2009.1012 [doi]
AB  - Cyclosporin A (CsA) has recently been proposed for use in the early phase after 
      traumatic brain injury (TBI), for its ability to preserve mitochondrial integrity 
      in experimental brain injury models, and thereby provide improved behavioral 
      outcomes as well as significant histological protection. 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 h of the injury patients 
      received 5 mg/kg of CsA infused over 24 h, 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 h, 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 h and for WBC counts at 24 h 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 mg/kg, infused over 24 h, during the early 
      phase after severe head injury in humans, with the aim of neuroprotection.
FAU - Mazzeo, Anna Teresa
AU  - Mazzeo AT
AD  - Department of Neurosciences, Psychiatric and Anesthesiological Sciences, 
      University of Messina , Messina, Italy.
FAU - Brophy, Gretchen M
AU  - Brophy GM
FAU - Gilman, Charlotte B
AU  - Gilman CB
FAU - Alves, Oscar Luis
AU  - Alves OL
FAU - Robles, Jaime R
AU  - Robles JR
FAU - Hayes, Ronald L
AU  - Hayes RL
FAU - Povlishock, John T
AU  - Povlishock JT
FAU - Bullock, M Ross
AU  - Bullock MR
LA  - eng
GR  - NS12587/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Placebos)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anti-Inflammatory Agents/administration & dosage/adverse effects/pharmacokinetics
MH  - Biomarkers
MH  - Blood Urea Nitrogen
MH  - Brain Injuries/*drug therapy/mortality/*physiopathology
MH  - Creatinine/blood
MH  - Cyclosporine/*administration & dosage/adverse effects/pharmacokinetics
MH  - Double-Blind Method
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Enzyme Inhibitors/administration & dosage/adverse effects/pharmacokinetics
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/adverse effects/pharmacokinetics
MH  - Kidney/drug effects
MH  - Leukocyte Count
MH  - Male
MH  - Middle Aged
MH  - Neuroprotective Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Placebos
MH  - Prospective Studies
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC2824218
EDAT- 2009/07/23 09:00
MHDA- 2010/03/24 06:00
PMCR- 2010/12/01
CRDT- 2009/07/23 09:00
PHST- 2009/07/23 09:00 [entrez]
PHST- 2009/07/23 09:00 [pubmed]
PHST- 2010/03/24 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - 10.1089/neu.2009.1012 [pii]
AID - 10.1089/neu.2009.1012 [doi]
PST - ppublish
SO  - J Neurotrauma. 2009 Dec;26(12):2195-206. doi: 10.1089/neu.2009.1012.