title: Translational pharmacokinetics: challenges of an emerging approach to drug development in stroke.
abstract: BACKGROUND
  There is increasing recognition of the importance of translational pharmacokinetics in stroke research, lack of which has been cited as one of the main contributing factors to failure of Phase III trials.
  
  
  METHODS
  The article reviews the translational issues in administration, distribution and sampling in the pharmacokinetics of putative therapeutic drugs in stroke. In addition, the role of translational pharmacometrics in drug development is discussed. The review uses the anti-inflammatory agent, IL-1 receptor antagonist, as an example. The reader will gain an insight into the pitfalls that are commonplace in translating pharmacokinetics from the preclinical to the clinical scenario. The reader will also gain an understanding of the complexities of blood-central nervous system (CNS) barriers in relation to brain pharmacokinetics and the increasing use of translational pharmacometrics in stroke research.
  
  
  CONCLUSIONS
  The translation of preclinical to clinical pharmacokinetics is a discipline that is traditionally overlooked and is likely to be a key factor responsible for failure of clinical trials. With a clear comprehensive insight into the benefits and limitations of translational pharmacokinetics in stroke, translational pharmacokinetics can be safely used to enhance the efficacy of clinical trials in stroke and their likelihood of success.
authors.affiliation: Manchester Academic Health Sciences Centre (MAHSC), Faculty of Life Sciences, AV Hill Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Greenhalgh
authors.forename: Kayode
authors.initials: K
authors.lastname: Ogungbenro
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Rothwell
authors.forename: James P
authors.initials: JP
authors.lastname: Galea
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D004341:Drug Evaluation; D057510:Endovascular Procedures; D006801:Humans; D057967:Infusions, Intraventricular; D055104:Infusions, Subcutaneous; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D018696:Neuroprotective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D049268:Positron-Emission Tomography / Q000379:methods; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D020521:Stroke / Q000134:cerebrospinal fluid / Q000188:drug therapy*
chemical_list: D018696:Neuroprotective Agents; D017472:Receptors, Interleukin-1