Anti-thrombotic effect and pharmacokinetics of a novel factor Xa inhibitor Bg115-2 in mice / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVETo evaluate antithrombotic efficacy and preliminary pharmacokinetics of Bg115-2.METHODSProthrombin 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.RESULTSBg115-2 (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.CONCLUSIONBg115-2 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.