【摘要】 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。更多还原

【Abstract】 AIM To study and compare pharmacokinetics (PK) afte r epidural or intravenous (iv) administration of [ 125 I]labeled Huwento xin-1 ([ 125 I]HWTX-1) in rhesus monkeys. METHODS H uwentoxin-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 (L 3) and the forth lumbar (L 4) interspaces using a 12-gauge paracentetic needle into epidural sp ace of rhesus monkeys or iv at the same dose. Reverse Phase High Performance Liq uid Chromatography (RP-HPLC) determined serum [ 125 I]Huwentoxin-1 w ith an automatic gamma counter. RESULTS The puriation of [ 125 I]Huwentoxin-1>96% and with the same bio-activity as unlabeled Huwen toxin-1; Radioactivity detected in epidural space was 38% of injected radioacti vity at 10 min after epidural injection, which demonstrated successful administr ation into epidural space; The maximum serum concentration after epidural or iv administration of [ 125 I]labeled Huwentoxin-1 were determined to be (0 70±0 04) MBq·L -1 and (4 98±0 58) MBq·L -1 , respectively, a t the maximum serum concentration times of 30 min and 2 min. Terminal T 1/2 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 a dministration was(95±5)%. CONCLUSION Concentration-time cur ves of [ 125 I] 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.更多还原