A kinetic analysis of fibrinogenolysis during plasminogen activator therapy.
Clin Pharmacol Ther
; 41(3): 297-303, 1987 Mar.
Article
em En
| MEDLINE
| ID: mdl-3102144
ABSTRACT
A mathematic model of the systemic fibrinogenolysis that accompanies coronary thrombolysis with recombinant tissue plasminogen activator (rt-PA) has been devised. The kinetic parameters of the model were estimated by nonlinear regression analysis with data from a clinical trial of rt-PA. The plasma elimination rate constant for rt-PA was estimated to be 10.0 hr-1, the second-order catalytic rate constant for the in vivo rt-PA-mediated conversion of plasminogen to plasmin 0.0078 (microgram rt-PA/kg body weight)-1 hr-1, the plasma elimination rate constant for plasmin 2.33 hr-1, and the second-order catalytic rate constant for the in vivo plasmin-catalyzed degradation of fibrinogen 0.466 (mg plasmin/dl)-1 hr-1. Computer simulation studies based on these parameter estimates show that the magnitude of fibrinogenolysis induced by rt-PA is related to the dose in a curvilinear fashion, showing diminishing increments in the effect at increasing doses. The degree of fibrinogenolysis induced by rt-PA administration is nearly independent of the dosing schedule.
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Base de dados:
MEDLINE
Assunto principal:
Fibrinogênio
/
Ativador de Plasminogênio Tecidual
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
1987
Tipo de documento:
Article