P. Tanswell et al., PHARMACOKINETICS OF DEGRADATION PRODUCTS OF FIBRIN AND FIBRINOGEN DURING ALTEPLASE THERAPY OF ACUTE MYOCARDIAL-INFARCTION, Fibrinolysis, 7(6), 1993, pp. 408-415
Pharmacokinetics of fibrin degradation products (FbDP), D-dimers, fibr
inogen degradation products (FgDP) and total degradation products (TDP
) in plasma were investigated using ELISA methods in 12 patients under
going therapy with alteplase (100 mg/3 h) for acute myocardial infarct
ion. Peak concentrations of all degradation products occurred signific
antly later (1.6-2.5h) than peak alteplase levels (2 min). Peak D-dime
r concentrations (mean 2.6 mug/ml) were significantly lower than those
of FbDP (7.1 mug/ml) or FgDP (7.8 mug/ml). However, the half-life of
D-dimers (mean 13.3 h) was more than 4.5-fold longer than that of FbDP
(2.9 h) or FgDP (2.8 h) (p<0.001). Consequently, areas under the plas
ma concentration-time curve (AUC) of D-dimers were comparable with tho
se of FbDP or FgDP. The ratios AUC(FbDP)/AUC(FgDP) and AUC(D-dimers)/A
UC(FgDP) are proposed as new indices of fibrin specificity. Their valu
es in this study (geometric mean, 95 % CI) were 1. 15 (0.60-2.20) and
1.30 (0.52-3.24) respectively. It is concluded that cross-linking may
prolong the half-life of fibrin degradation products, and that complet
e time profiles of fibrin- and fibrinogen degradation products in plas
ma, rather than single point measurements, are essential for reliable
quantification of fibrin specificity.