Anti-thrombotic effect and pharmacokinetics of a novel factor Xa inhibitor Bg115-2 in mice
- Author:
- No author available
- Journal Title:
- Chinese Journal of Pharmacology and Toxicology
- Issue:
- 1
- DOI:
- 10.3867/j.issn.1000-3002.2012.01.003
- Key Word:
- Bg115-2;血液凝固;因子Xa;抑制素类;血栓形成;药代动力学;Bg115-2;blood coagulation;factor X a;inhibins;thrombosis;pharmacokinetics
Abstract： OBJECTIVE To evaluate antithrombotic efficacy and preliminary pharmacokinetics of Bg115-2.METHODS Prothrombin time (PT) and activated partial thromboplastin time (APTT) in vitro were determined using assay kits,respectively.The effect on venous thrombosis was evaluated with the model of inferior sinus venous thrombosis in mice.Bleeding reaction was measured by tail bleeding time test.Preliminary pharmacokinetic study was conducted using FXa activity assay.RESULTS Bg115-2 (sc) 0.75 -3.0 mg·kg-1 prolonged PT (P＜0.05,P＜0.01) and APTT (P ＜ 0.01) dose-dependently. In the inferior sinus venous thrombosis model,Bg115-20.19 - 3.0 mg· kg-1 significantly reduced thrombus mass with ID50 of 0.19 mg· kg-1.Interestingly,Bg115-2 (ig) 1.5 -6.0 mg·kg-1 also significantly reduced venous thrombus mass (P ＜0.01 ).Bg115-2 was similar to nadroparin calcium in bleeding reaction,and ED2/ID50 reached up to 26.8.Furthermore,Bg115-2 3.0 mg· kg-1 displayed a pharmacokinetic character with a two-compartment model.t1/2,cmax and AUC were (6.18 + 1.45 ) h,(5.20 + 0.66) mg·L-1 and (43.75 +8.20)mg·L-1 ·h,respectively.CONCLUSION Bg115-2 is a potent and oral effective inhibitor of venous thrombosis in mice with slight bleeding side-effect.It has longer t1/2 and the distribution character of a twocompartment model.
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