title: A clinically relevant review of tizanidine hydrochloride dose relationships to pharmacokinetics, drug safety and effectiveness in healthy subjects and patients.
abstract: OBJECTIVE
  Tizanidine, one of the few oral antispastic therapies approved for use in the USA, has a narrow therapeutic index that can often make optimal patient dosing difficult. We surveyed the published literature for data on potential tizanidine dose relationships to pharmacokinetics, drug safety and effectiveness, as well as to provide practical drug dosing advice.
  
  
  RESULTS
  The number of primary studies that describe tizanidine dose proportionality relationships was somewhat limited, even when including studies that used doses above those currently recommended or data from drug-drug interaction studies that resulted in supra-therapeutic tizanidine concentrations.
  
  
  CONCLUSIONS
  There is substantial evidence to show that plasma tizanidine concentrations are linearly related to dose in healthy subjects and patients, although there is a high degree of intersubject variability. The most common adverse events and pharmacodynamic effects are related to plasma concentrations. The clinical implications of the large interpatient variability in plasma tizanidine concentrations and its narrow therapeutic index make it necessary to individualise patient therapy. Practical advice on tizanidine dosing and/or switching between formulations is provided.
authors.affiliation: Medical Affairs Department, Acorda Therapeutics, Inc., Hawthorne, NY, USA. hhenney@acorda.com
authors.forename: H R
authors.initials: HR
authors.lastname: Henney
authors.forename: J D
authors.initials: JD
authors.lastname: Runyan
mesh_terms: D002626:Chemistry, Pharmaceutical; D002939:Ciprofloxacin / Q000494:pharmacology; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016666:Fluvoxamine / Q000494:pharmacology; D006801:Humans; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy; D009125:Muscle Relaxants, Central / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016896:Treatment Outcome
chemical_list: D009125:Muscle Relaxants, Central; D002939:Ciprofloxacin; C023754:tizanidine; D003000:Clonidine; D016666:Fluvoxamine