title: Clinical relevance of pharmacological and physiological data in intrathecal baclofen therapy.
abstract: OBJECTIVE
  To review all pharmacological and physiological data available on intrathecal baclofen (ITB) therapy and to evaluate its use in clinical practice and future research.
  
  
  METHODS
  PubMed was searched for relevant anatomic, physiological, and pharmacological data available on ITB.
  
  
  METHODS
  All currently available data on ITB pharmacokinetics (PKs) and pharmacodynamics (PDs) in both human and animal studies were reviewed and combined with the anatomy and physiology of the intrathecal space and cerebrospinal fluid flow.
  
  
  METHODS
  Only 4 studies reported PK data on ITB in humans. More studies reported PD data on ITB; however, none were combined with PK data. More detailed data on PK could be gathered from studies using an animal model.
  
  
  RESULTS
  ITB does not spread equally over the intrathecal space after injection, but it diffuses according to a concentration gradient. ITB distribution can be influenced by the location of the catheter tip and by changing the infusion mode.
  
  
  CONCLUSIONS
  The pharmacological and physiological data on ITB can be used to support decisions in clinical practice concerning drug concentration, infusion regimens, localization of the catheter tip, and management of tolerance; however, some strategies have little evidence in humans.
authors.affiliation: Department of Neurosurgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: h.w.heetla@umcg.nl.
authors.forename: Herre W
authors.initials: HW
authors.lastname: Heetla
authors.affiliation: Department of Neurosurgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Michiel J
authors.initials: MJ
authors.lastname: Staal
authors.affiliation: Department of Pharmacokinetics, Toxicology and Targeting, University Centre for Pharmacy, University of Groningen, Groningen, The Netherlands; Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Proost
authors.affiliation: Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Teus
authors.initials: T
authors.lastname: van Laar
mesh_terms: D000818:Animals; D001418:Baclofen / Q000493:pharmacokinetics* / Q000494:pharmacology; D004361:Drug Tolerance; D058786:GABA-B Receptor Agonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D060186:Infusions, Spinal / Q000379:methods*; D009128:Muscle Spasticity / Q000188:drug therapy / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism
chemical_list: D058786:GABA-B Receptor Agonists; D001418:Baclofen
keywords: Baclofen; Cerebrospinal fluid; Drug tolerance; Injections, spinal; Pharmacokinetics; Pharmacology; Rehabilitation