CAJ | 학술논문

目的比较大鼠硬膜外注射或iv [125I]虎纹毒素-1([125I]HWTX-1)后的药代动力学和组织分布.方法用Iodogen法标记HWTX-1.大鼠经硬膜外腔插管或尾静脉注射给药.反相高效液相色谱法在线检测体液中[125I]HWTX-1浓度; γ-计数仪测定组织放射性.结果硬膜-脊椎样品放射性为注射放射性的(22±8)%,表明硬膜外注射成功.两给药途径的药时曲线不同: 硬膜外给药存在吸收相, 10 min达峰; cmax和AUC随剂量递增; 大鼠硬膜外和iv后, [125I]降解产物的浓度分别为(2.1±1.1)和(6.8±2.5)μg·L-1(P<0.01); 末端t1/2分别为2.5～2.8 h和2.3 h; ClS为0.74～1.18 L·h-1·kg-1.硬膜外给予[125I]HWTX-1的生物利用度>82%.两给药途径的分布不同: iv后10 min, 大多数组织药物暴露水平高于硬膜外给药(P<0.05).放射性主要经尿排泄.结论两种注射途径的放射性在不同组织中的生物分布及药物降解等差异支持了HWTX-1经硬膜外注射用作镇痛药.
목적비교대서경막외주사혹iv [125I]호문독소-1([125I]HWTX-1)후적약대동역학화조직분포.방법용Iodogen법표기HWTX-1.대서경경막외강삽관혹미정맥주사급약.반상고효액상색보법재선검측체액중[125I]HWTX-1농도; γ-계수의측정조직방사성.결과경막-척추양품방사성위주사방사성적(22±8)%,표명경막외주사성공.량급약도경적약시곡선불동: 경막외급약존재흡수상, 10 min체봉; cmax화AUC수제량체증; 대서경막외화iv후, [125I]강해산물적농도분별위(2.1±1.1)화(6.8±2.5)μg·L-1(P<0.01); 말단t1/2분별위2.5～2.8 h화2.3 h; ClS위0.74～1.18 L·h-1·kg-1.경막외급여[125I]HWTX-1적생물이용도>82%.량급약도경적분포불동: iv후10 min, 대다수조직약물폭로수평고우경막외급약(P<0.05).방사성주요경뇨배설.결론량충주사도경적방사성재불동조직중적생물분포급약물강해등차이지지료HWTX-1경경막외주사용작진통약.
AIM To compare pharmacokinetics and tissue-distribution after epidural and iv administration of [125I]labelled huwentoxin-1 ([125I]HWTX-1) in rats. METHODS HWTX-1 was labeled by iodogen method. Single dose of 0.86, 1.7, or 2.6 MBq [125I]HWTX-1 per rat was injected via a catheter implanted in epidural space or iv with single dose of 2.6 MBq per rat. Serum [125I]HWTX-1 was determined by RP-HPLC with flow scintillation detector. Tissue radioactivity was detected by γ-counter. RESULTS Radioactivities detected in dural-vertebral samples was (22±8)% of injected radioactivity at 10 min after epidural injection, which demonstrated successful administration into epidural space. Concentration-time curves of [125I]HWTX-1 after two routes were different. Absorption phase with tmax at 10 min was observed after epidural injection. 125I-labeled degradation products at 10 min after epidural and iv injection of 2.6 MBq were (2.1±1.1) and (6.8±2.5)μg·L-1, respectively (P<0.01). cmax and AUC were increased with dose after epidural administration. Terminal t1/2 after epidural or iv administration was 2.5-2.8 h or 2.3 h. ClS was 0.74-1.18 L·h-1·kg-1 after both routes. Bioavailability after epidural administration was >82%. Distribution of [125I]HWTX-1 between two routes was different, and contents in most tissues at 10 min after iv were higher than those after epidural dosing (P<0.05). Excretion of radioactivity was mainly via urine. CONCLUSIONThe differences between vertebral and systemic biodistribution of HWTX-1, as well as degradation profiles after epidural and iv injection support the using of HWTX-1 as analgesic by epidural administration.