中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2012年
1期
10-15
,共6页
杨健%朱亚楠%刘晓岩%王银叶
楊健%硃亞楠%劉曉巖%王銀葉
양건%주아남%류효암%왕은협
Bg115-2%血液凝固%因子Xa%抑制素类%血栓形成%药代动力学
Bg115-2%血液凝固%因子Xa%抑製素類%血栓形成%藥代動力學
Bg115-2%혈액응고%인자Xa%억제소류%혈전형성%약대동역학
Bg115-2%blood coagulation%factor X a%inhibins%thrombosis%pharmacokinetics
目的 探讨Bg115-2的抗血栓功效和初步药代动力学性质.方法 试剂盒测定小鼠半体内凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)；采用小鼠下腔静脉结扎模型评价对静脉血栓的作用；采用尾尖测定出血时间法；用FXa活性测定Bg115-2的血药浓度.结果 sc给予Bg115-2 0.19 ～3.0 mg·kg-1可明显地、剂量依赖地延长PT (P ＜0.05,P＜0.01)和ApTT (P ＜0.01)；Bg115-2 0.75 ～3.0 mg·kg-1可显著地减轻血栓质量,其抑制50％血栓形成的剂量(ID50)为0.19 mg·kg-1；ig给予Bg115-2 1.5 ～ 6.0 mg·kg -也明显地减轻血栓质量(P＜0.01).Bg1 15-2的出血反应与那曲帕林钙相似,有较高的出血风险效益比,ED2/ID50为26.8.另外单次sc给予Bg115-2 3.0 mg·kg-1显示出二室模型的药代动力学特点,t1/2为(6.18±1.45)h,cmax为(5.20 +0.66) mg·L-1,AUC为(43.75±8.20)mg·L-1·h.结论 Bg115-2为一注射和口服均可的、强效的静脉血栓形成抑制剂,出血不良作用较轻.它具有较长的半衰期和二室模型的分布特征.
目的 探討Bg115-2的抗血栓功效和初步藥代動力學性質.方法 試劑盒測定小鼠半體內凝血酶原時間(PT)和活化部分凝血活酶時間(APTT)；採用小鼠下腔靜脈結扎模型評價對靜脈血栓的作用；採用尾尖測定齣血時間法；用FXa活性測定Bg115-2的血藥濃度.結果 sc給予Bg115-2 0.19 ～3.0 mg·kg-1可明顯地、劑量依賴地延長PT (P ＜0.05,P＜0.01)和ApTT (P ＜0.01)；Bg115-2 0.75 ～3.0 mg·kg-1可顯著地減輕血栓質量,其抑製50％血栓形成的劑量(ID50)為0.19 mg·kg-1；ig給予Bg115-2 1.5 ～ 6.0 mg·kg -也明顯地減輕血栓質量(P＜0.01).Bg1 15-2的齣血反應與那麯帕林鈣相似,有較高的齣血風險效益比,ED2/ID50為26.8.另外單次sc給予Bg115-2 3.0 mg·kg-1顯示齣二室模型的藥代動力學特點,t1/2為(6.18±1.45)h,cmax為(5.20 +0.66) mg·L-1,AUC為(43.75±8.20)mg·L-1·h.結論 Bg115-2為一註射和口服均可的、彊效的靜脈血栓形成抑製劑,齣血不良作用較輕.它具有較長的半衰期和二室模型的分佈特徵.
목적 탐토Bg115-2적항혈전공효화초보약대동역학성질.방법 시제합측정소서반체내응혈매원시간(PT)화활화부분응혈활매시간(APTT)；채용소서하강정맥결찰모형평개대정맥혈전적작용；채용미첨측정출혈시간법；용FXa활성측정Bg115-2적혈약농도.결과 sc급여Bg115-2 0.19 ～3.0 mg·kg-1가명현지、제량의뢰지연장PT (P ＜0.05,P＜0.01)화ApTT (P ＜0.01)；Bg115-2 0.75 ～3.0 mg·kg-1가현저지감경혈전질량,기억제50％혈전형성적제량(ID50)위0.19 mg·kg-1；ig급여Bg115-2 1.5 ～ 6.0 mg·kg -야명현지감경혈전질량(P＜0.01).Bg1 15-2적출혈반응여나곡파림개상사,유교고적출혈풍험효익비,ED2/ID50위26.8.령외단차sc급여Bg115-2 3.0 mg·kg-1현시출이실모형적약대동역학특점,t1/2위(6.18±1.45)h,cmax위(5.20 +0.66) mg·L-1,AUC위(43.75±8.20)mg·L-1·h.결론 Bg115-2위일주사화구복균가적、강효적정맥혈전형성억제제,출혈불량작용교경.타구유교장적반쇠기화이실모형적분포특정.
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.
