猕猴硬膜外及静脉注射 [~(125)I]虎纹毒素-1的药代动力学(英文)

目的　研究与比较猕猴硬膜外 (ed)及静脉 (iv)注射虎纹毒素 1后的药代动力学过程。方法　Iodogen法标记虎纹毒素 1 ,按 0 388MBq·kg- 1 的剂量向猕猴第 3和第 4腰椎之间硬膜外腔及静脉注射标记后虎纹毒素 1 ,用反相高效液相色谱检测猴血清中的药物放射性活度 ;γ 计数仪检测猴第 3和第 4腰椎硬膜外腔的药物放射性活度。结果　制备了具有生物活性的 [1 2 5I]虎纹毒素 1。硬膜外给药 1 0min后 ,给药部位局部硬膜外腔的药物放射性占总给药量的0 38,说明硬膜外给药是成功的 .硬膜外及静脉给药后 ,血药浓度分别在 30min和 2min达峰 ,分别为 (0 70± 0 0 4 )MBq·L- 1 和 (4 98± 0 58)MBq·L- 1 。两种给药途径的药时曲线不同 :猕猴硬膜外和静脉给药后 ,末端T12 分别为(1 0 36± 0 2 7)h和 (1 1 0 3± 1 1 6)h ;ClS 分别为 (1 2 9±0 0 7)L·h- 1 ·kg- 1 和 (1 2 5± 0 2 3)L·h- 1 ·kg- 1 ,硬膜外给予 [1 2 5I]HWTX 1的绝对生物利用度 (95± 5) %。结论　硬膜外和静脉两种给药方式下 ,[1 2 5I]虎纹毒素 1在猕猴体内的药代动力学过程具有差异性 ,两种给药方式下 [1 2 5I]在猕猴体内的分布与吸收特点对于虎纹毒素 I的临床药效学和毒理学研究提供了参考数据。

Pharmacokinetics of [125I]Huwentoxin-1 after epidural and intravenous administration to rhesus monkeys

AIM To study and compare pharmacokinetics (PK) after epidural or intravenous (iv) administration of [125I]labeled Huwentoxin-1 ([125I]HWTX-1) in rhesus monkeys. METHODS Huwentoxin-1 was labeled by iodogen method and was administered at a dose of 0.388 MBq*kg-1 by lumbar puncture at the third lumbar (L3) and the forth lumbar (L4) interspaces using a 12-gauge paracentetic needle into epidural space of rhesus monkeys or iv at the same dose. Reverse Phase High Performance Liquid Chromatography (RP-HPLC) determined serum [125I]Huwentoxin-1 with an automatic gamma counter. RESULTS The puriation of [125I]Huwentoxin-1>96% and with the same bio-activity as unlabeled Huwentoxin-1; Radioactivity detected in epidural space was 38% of injected radioactivity at 10 min after epidural injection, which demonstrated successful administration into epidural space; The maximum serum concentration after epidural or iv administration of [125I]labeled Huwentoxin-1 were determined to be (0.70±0.04) MBq*L-1 and (4.98±0.58) MBq*L-1, respectively, at the maximum serum concentration times of 30 min and 2 min. Terminal T1/2 after epidural or iv administration were (10.36±0.27) h or (11.03±1.16) h, respectively. Cls was (1.29±0.07) L*h-1*kg-1 or (1.25±0.23) L*h-1*kg-1, respectively. Bioavailability after epidural administration was(95±5)%. CONCLUSION Concentration-time curves of [125I] labeled Huwentoxin-1 after two routes were different. The degradation profiles after epidural and iv injection supported the using of HWTX-1 as analgesic by epidural administration.