Global anticoagulant effects of a synthetic anti-factor Xa inhibitor (DX-9065a): Implications for interventional use
Küçük Resim Yok
Tarih
2003
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Westminster Publ Inc
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Heparin has been conventionally used as an anticoagulant for medical and surgical indications. Because factor Xa is an essential component of the prothrombinase complex and leads to the generation of thrombin, its inhibition has become a focus of newer antithrombotic drug development. The in vitro anticoagulant profile of DX-9065a, a synthetic direct factor Xa inhibitor, was studied using activated clotting time assay, thrombelastography, and global clotting tests, such as prothrombin time (PT), activated partial thromboplastin time (aPTT), diluted aPTT, Heptest, Heptest-HI, dilute Russell's viper venom time (dRVVT), thrombin time, ecarin clotting time, and amidolytic anti-Xa assay. In addition, the effect of DX-9065a on platelet aggregation and inhibition of thrombin generation markers (FPA, F1 + 2, and TAT) were studied. The pharmacokinetic and pharmacodynamic profiles of DX-9065a were also studied in a non-human primate (Macaca mulatta) model. DX-9065a produced a concentration-dependent increase in the Hemochron celite ACT and HemoTec ACT. Clotting times of 538 19 and 401 12, respectively, were reached at a concentration of 25 mug/mL signifying that DX-9065a may be useful in interventional cardiological procedures. DX-9065a prolonged the r-time on thrombelastography. DX-9065a did not show any effect on adenosine diphosphate (ADP)-, collagen-, epinephrine-, and arachidonic acid-induced platelet aggregation at concentrations up to 10 mug/mL. DX-9065a exhibited a concentration-dependent prolongation of the PT, aPTT, diluted aPTT, Heptest, dRVVT, and reached the clotting times of 51.6, 132, 193, 47.9, 129.9 seconds, respectively, at a final concentration of 12.5 mug/mL; compared to a control value of 10.6, 30.2, 41.9, 14, 32.2 seconds, respectively. DX-9065a did not affect the ecarin clotting time and thrombin time at concentrations up to 12.5 mg/mL. Because DX-9065a prolonged the dRVVF, this may impact diagnostic screening of patients with systemic lupus erythematosus.
Açıklama
Anahtar Kelimeler
factor Xa inhibitor, clot-based assays, amidolytic anti-Xa assay, thrombin generation markers, platelet aggregation, pharmacokinetics
Kaynak
Clinical and Applied Thrombosis-Hemostasis
WoS Q Değeri
Q3
Scopus Q Değeri
Cilt
9
Sayı
1
