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首页> 外文期刊>Life sciences >CEREBROSPINAL FLUID DISTRIBUTION OF OPIOIDS AFTER INTRAVENTRICULAR AND LUMBAR SUBARACHNOID ADMINISTRATION IN SHEEP
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CEREBROSPINAL FLUID DISTRIBUTION OF OPIOIDS AFTER INTRAVENTRICULAR AND LUMBAR SUBARACHNOID ADMINISTRATION IN SHEEP

机译：绵羊脑室内和腰椎蛛网膜下腔给药后阿片样物质的脑脊髓液分布

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The study of opioid distribution in blood and cerebrospinal fluid (CSF) is required to understand pharmacokinetic-pharmacodynamic relationships following lumbar intrathecal (it) and intracerebroventicular (icy) adminis- tration, and to investigate the contributions of spinal or supraspinal sites of action. The sheep model developed for pharmacokinetic study of anal- gesics allows atraumatic sampling of plasma and CSF after drug adminis- tration by the intravenous (iv), icy, and it routes in an unanesthetized animal. Five adult female sheep were prepared with femoral vascular catheters, lumbar it and epidural cannulae, icv cannulae, and cisterna magna cannulae. Hydromorphone, methadone, naloxone, and [C-14] sucrose were injected and collected by two methods: 1) injection into the icy cannula with lumbar CSF samples collected via the lumbar cannula and 2) injection into the lumbar cannula and cisternal CSF samples collected via ventriculocisternal cannula. Hydromorphone, morphine, and [C-14] sucrose were detected at 90-105 min in lumbar CSF after icy injection. Hydromorphone and [C-14] sucrose were detected in icy cerebrospinal fluid at 50 min after lumbar it injection. Methadone was not detected in icy cereb- rospinal fluid after it injection, nor was methadone significantly detected in lumbar CSF after icy injection. These data indicate that icy and it administration of lipophilic opioids produces CSF distributions different from those of hydrophilic opioids. This suggests that lipophilic opioids such as methadone or naloxone exert their effects predominantly on tissues near the site of injection. The study of it and icy opiate administration and CSF pharmacokinetics may therefore have direct clinical implications. [References: 32]
机译：需要了解阿片样物质在血液和脑脊液（CSF）中的分布，以了解在腰椎鞘内（it）和脑室内（icy）给药后的药代动力学与药效关系，并研究脊柱或脊髓上动作部位的作用。为镇痛药的药代动力学研究而开发的绵羊模型可在静脉内（iv）冰冷给药后，对血浆和CSF进行无创取样，并在未麻醉的动物中进行。准备五只成年雌性绵羊，用股血管导管，腰椎和硬膜外插管，icv插管和大水罐插管。注射并收集氢吗啡酮，美沙酮，纳洛酮和[C-14]蔗糖：两种方法：1）通过腰部套管收集的腰部CSF样品注入冰套管中，以及2）收集到腰部套管和胸骨的CSF样品中通过心室胸骨内部插管。冰冷注射后90-105分钟在腰部CSF中检测到氢吗啡酮，吗啡和[C-14]蔗糖。腰部注射50分钟后，在冰冷的脑脊液中检测到氢吗啡酮和[C-14]蔗糖。注射后冰冷的脑脊髓液中未检出美沙酮，注射后的腰部CSF中也未检出美沙酮。这些数据表明，亲脂性阿片类药物的冰冷及其给药产生的CSF分布不同于亲水性阿片类药物。这表明诸如美沙酮或纳洛酮的亲脂性阿片样物质主要在注射部位附近的组织上发挥作用。因此，对它的研究以及冰镇阿片给药和CSF药代动力学可能具有直接的临床意义。 [参考：32]

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