The effects of age and gender on the pharmacokinetics and pharmacodynamics in healthy subjects of the plasminogen activator, lanoteplase.

AIMS: 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.

Comparison of pharmacokinetics of lanoteplase and alteplase during acute myocardial infarction.

OBJECTIVE: Lanoteplase is a rationally designed variant of tissue plasminogen activator. The aim of this study was to examine the pharmacokinetics and functional activity of a single intravenous bolus dose of lanoteplase with those of a bolus plus two-step infusion of alteplase. DESIGN: Seven-centre substudy of the InTIME-I angiographic trial in patients presenting within 6 hours of onset of suspected acute myocardial infarction. PATIENTS AND PARTICIPANTS: A total of 31 patients (28 males, 3 females) enrolled in this substudy [mean age 59 (range 26 to 76) years]. METHODS: Twenty-three patients randomised to lanoteplase received single bolus doses of 15 kU/kg (n = 5), 30 kU/kg (n = 3), 60 kU/kg (n = 9), or 120 kU/kg (n = 6). Eight patients received alteplase