大鼠硬膜外和静脉注射 [~(125)I]虎纹毒素-1后的药代动力学(英文)

目的　比较大鼠硬膜外注射或iv [12 5I]虎纹毒素 1([12 5I]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 [12 5I]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 (2 2± 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 ,10min达峰 ;cmax 和AUC随剂量递增 ;大鼠硬膜外和iv后 ,[12 5I]降解产物的浓度分别为 (2 .1± 1.1)和(6 .8± 2 .5 ) μg·L- 1(P <0 .0 1) ;末端t1/2 分别为2 .5～ 2 .8h和 2 .3h ;ClS 为 0 .74～ 1.18L·h- 1·kg- 1。硬膜外给予 [12 5I]HWTX 1的生物利用度 >82 %。两给药途径的分布不同 :iv后 10min ,大多数组织药物暴露水平高于硬膜外给药 (P <0 .0 5 )。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。

Pharmacokinetic profiles of huwentoxin-1 after epidural and intravenous administration in rats

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.