title: Pharmacokinetics of  alteplase  in the treatment of ischaemic stroke.
abstract: BACKGROUND
  Alteplase is the only approved drug for thrombolysis in acute ischaemic stroke (AIS) after its initial use in acute myocardial infarction (AMI). Its role in functional recovery is time-dependent while its major adverse effect, intracranial haemorrhage, is dose-dependent. These underline the importance of the pharmacokinetics of alteplase to its clinical use.
  
  
  METHODS
  The authors discuss the pharmacology of alteplase with a major focus on its pharmacokinetics based on literature obtained from the OVID electronic database and other institutional resources.
  
  
  CONCLUSIONS
  The pharmacokinetic profile of alteplase is almost entirely derived from studies in AMI. Differences in the pathophysiology of AMI and AIS mean it cannot be assumed that the pharmacokinetics of alteplase is similar in these two populations. During AMI, cardiac function and, hence, hepatic perfusion and clearance of alteplase may be impaired. The relatively older population in AIS may have impaired metabolic clearance which may increase plasma concentrations. The concurrent use of medications such as nitrates in the management of elevated blood pressure during AIS thrombolysis is also associated with reduced plasma concentrations of alteplase. Again, differences in clot size and type between AMI and AIS and between subtypes of AIS may influence response to alteplase. There is an inherently higher risk of intracranial haemorrhage in AIS compared to AMI emanating from cerebral infarction and BBB disruption. Accordingly, stroke-specific pharmacokinetics of alteplase and its relationship to efficacy and safety outcomes are required.
authors.affiliation: Acute Stroke Service, Newcastle Upon Tyne Hospitals NHS Foundation Trust, England, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Acheampong
authors.forename: Gary A
authors.initials: GA
authors.lastname: Ford
mesh_terms: D002545:Brain Ischemia / Q000188:drug therapy*; D004347:Drug Interactions; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics*; D006801:Humans; D011358:Product Surveillance, Postmarketing; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator