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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。
Objective To compare the pharmacokinetics and tissue distribution of epidural injections or iv [125I] tiger toxin 1 ([125I] HWTX 1) in rats. Methods HWTX 1 was labeled by Iodogen method. Rats were administered by epidural catheter or tail vein injection. On-line detection of [125 I] HWTX 1 concentrations in body fluids by reverse-phase high performance liquid chromatography; Tissue radioactivity was measured with a gamma counter. Results The radioactivity of the dural samples was (2 2 ± 8)% of the injected radioactivity, indicating that the epidural injection was successful. The drug-delivery curves of the two routes were different: there was an absorption phase in the epidural administration, reaching a peak at 10 min; the cmax and AUC increased with dose; the concentrations of the [125 I] degradation products in the epidural and iv groups were 2 .1 ± 1.1) and (6 .8 ± 2.5) μg · L -1 (P <0.01) respectively. The terminal t 1/2 was 2.5 ~ 2.8 h and 2.3 h respectively. ClS was 0 .74 ~ 1.18L · h-1 · kg-1. Epidural administration [125I] HWTX 1 has a bioavailability of> 82%. The distribution of the two routes of administration varied: 10 min after iv, the level of drug exposure in most tissues was higher than that in the epidural administration (P <0.05). The main radioactive excretion of urine. Conclusions Differences in biodistribution and drug degradation of the two injection routes of radioactivity in different tissues support the use of HWTX 1 for epidural injection as an analgesic.