PHARMACOKINETICS OF DEGRADATION PRODUCTS OF FIBRIN AND FIBRINOGEN DURING ALTEPLASE THERAPY OF ACUTE MYOCARDIAL-INFARCTION

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.