title: The effects of age and gender on the pharmacokinetics and pharmacodynamics in healthy subjects of the plasminogen activator, lanoteplase.
abstract: OBJECTIVE
  To investigate the influence of age and gender on the intravenous pharmacokinetics and pharmacodynamics of the plasminogen activator, lanoteplase.
  
  
  METHODS
  Forty healthy subjects (10 each of young males, elderly males, young females and elderly females) received a single bolus 10 kU kg(-1) intravenous dose of lanoteplase. Plasma from blood serially collected for 24 h post-dose was analyzed for lanoteplase (antigen), fibrinogen, plasminogen and α2-antiplasmin concentrations, plasma plasminogen activation activity (PPAA) and rapid plasminogen activator inhibitor (PAI-1).
  
  
  RESULTS
  Lanoteplase mean total systemic clearance (CL(t)) values ranged from 1.9 to 2.8 l h(-1) and mean steady-state volume of distribution (V(ss)) values ranged from 12.3 to 15.6 l. Age-by-gender interactions were observed for lanoteplase CL(t) (P= 0.04), but no differences were observed for V(ss) or elimination half-life. Elderly females had a 27% lower mean CL(t) than young females (95% CI for the difference 0.17, 1.27 l h(-1)) and 32% lower CL(t) than elderly males (95% CI for the difference 0.15, 1.65 l h(-1)). PPAA AUC/dose values did not show an age-by-gender interaction. Haemostasis parameters indicated only a slight degree of systemic plasminogen activation.
  
  
  CONCLUSIONS
  Elderly females had a lower mean lanoteplase CL(t) than elderly males and young females. However, no difference was observed between young and elderly females for the AUC/dose of PPAA. In addition, there were no age-related or gender-related differences observed in the other pharmacodynamic parameters measured.
authors.affiliation: Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543-4000, USA.
authors.forename: Nimish N
authors.initials: NN
authors.lastname: Vachharajani
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Raymond
authors.forename: Wen-Chyi
authors.initials: WC
authors.lastname: Shyu
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Stouffer
authors.forename: David W
authors.initials: DW
authors.lastname: Boulton
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010960:Plasminogen Activators / Q000493:pharmacokinetics* / Q000494:pharmacology; D012737:Sex Factors; D010959:Tissue Plasminogen Activator / Q000493:pharmacokinetics* / Q000494:pharmacology; D055815:Young Adult
chemical_list: C081981:lanoteplase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator