Exposure of cyclosporin A in whole blood, cerebral spinal fluid, and brain extracellular fluid dialysate in adults with traumatic brain injury. J Neurotrauma 2013 Sep 01;30(17):1484-9
Date
04/02/2013Pubmed ID
23540442Pubmed Central ID
PMC3751213DOI
10.1089/neu.2012.2524Scopus ID
2-s2.0-84882724043 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Cyclosporin A (CsA), an immunosuppressive medication traditionally used in the prevention of post-transplant rejection, is a promising neuroprotective agent for traumatic brain injury (TBI). Preliminary studies in animals and humans describe the efficacy and safety of CsA when administered following neurotrauma. The objective of this study is to describe CsA exposure in adults with severe TBI by assessing concentrations in whole blood, cerebrospinal fluid (CSF), and brain extracellular fluid (ECF) dialysate as measured by brain microdialysis. Severe TBI patients were enrolled in a randomized controlled trial following the written informed consent of their legal guardians. Patients received either CsA 5 mg/kg as a continuous infusion over 24 h, or matching placebo. Noncompartmental exposure analyses were performed using CsA concentrations in whole blood, CSF, and ECF dialysate. There were 37 patients randomized to the CsA arm of the trial and included in this exposure analysis. CsA was detected in the ECF dialysate and CSF at a fraction of the whole blood concentration. Mean CsA maximum concentrations were achieved at 24 and 30 h from the start of the 24 h infusion, in the CSF and ECF dialysate, respectively. A correlation was found between ECF dialysate and CSF concentrations. CsA was detected in the blood, CSF, and brain ECF dialysate. CsA exposure characteristic differences exist for whole blood, CSF, and ECF dialysate in severe TBI patients when administered as a continuous intravenous infusion. These exposure characteristics should be used for safer CsA dose optimization to achieve target CsA concentrations for neuroprotection in future TBI studies.
Author List
Brophy GM, Mazzeo AT, Brar S, Alves OL, Bunnell K, Gilman C, Karnes T, Hayes RL, Bullock RAuthor
Kristen B. Bresnehan PharmD Assistant Professor in the School of Pharmacy Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Brain
Brain Injuries
Cyclosporine
Extracellular Fluid
Female
Humans
Infusions, Intravenous
Male
Microdialysis
Middle Aged
Neuroprotective Agents
Prospective Studies
Ventriculostomy
Young Adult
