The effects of age and gender on the pharmacokinetics and pharmacodynamics in healthy subjects of the plasminogen activator, lanoteplase.
Br J Clin Pharmacol
; 72(5): 775-86, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21545481
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Coagulação Sanguínea
/
Ativadores de Plasminogênio
/
Ativador de Plasminogênio Tecidual
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos