Propranolol reduces bupivacaine clearance.
Propranolol reduces bupivacaine clearance.
复制标题
普萘洛尔可降低布比卡因的清除率。
DOI：
10.1097/00000542-198701000-00007
复制
发表时间：
1987
期刊：
影响因子：
8.8
通讯作者：
John T. Slattery
中科院分区：
文献类型：
--
作者：
T. Bowdle;Peter R. Freund;John T. Slattery
普萘洛尔通过减少肝血流量和抑制利多卡因代谢来降低利多卡因的清除率。作者研究了普萘洛尔也降低布比卡因清除率的可能性。将30-50 mg布比卡因静脉内给予6名正常人志愿者，在10-15分钟内分两次，至少间隔2周。普萘洛尔，40毫克口服每6小时，使用一次，开始前24小时布比卡因管理。治疗的顺序是随机的。在36小时内采集22份静脉血样，以确定布比卡因清除率、终末消除速率常数和分布容积。所有受试者均出现轻度CNS毒性，包括耳鸣、面部刺痛或轻微视觉障碍，与静脉血浆峰浓度0.81 - 2.7 μ g/ml相关。对照组平均布比卡因清除率为0.33 +/- 0.12 l/min，普萘洛尔组为0.21 +/- 0.12 l/min，显著降低35%（P <0.01）。对照组的终末消除速率常数（β）为0.27 +/- 0.16 h-1，普萘洛尔组为0.14 +/- 0.069 h-1（P <0.05）;终末消除半衰期分别为2.6和4.9 h。分发量没有变化。由于布比卡因清除率对肝灌注相对不敏感，因此普萘洛尔似乎在肝细胞水平上对布比卡因代谢产生了实质性抑制。这些数据表明，合并使用普萘洛尔可能导致布比卡因蓄积毒性浓度。
Propranolol reduces the clearance of lidocaine by both reducing hepatic blood flow and inhibiting lidocaine metabolism. The authors investigated the possibility that propranolol reduces the clearance of bupivacaine as well. Bupivacaine, 30-50 mg, was administered intravenously to six normal human volunteers, over 10-15 min on two occasions, at least 2 weeks apart. Propranolol, 40 mg orally every 6 h, was used on one occasion, beginning 24 h prior to the bupivacaine administration. The sequence of the sessions was randomized. Twenty-two venous blood samples were obtained over 36 h in order to determine bupivacaine clearance, terminal elimination rate constant, and volume of distribution. All subjects experienced mild CNS toxicity, consisting of tinnitus, facial tingling, or subtle visual disturbances, associated with peak venous plasma concentrations of 0.81 to 2.7 micrograms/ml. Mean bupivacaine clearance was 0.33 +/- 0.12 l/min for the control session and 0.21 +/- 0.12 l/min during propranolol use, a significant 35% reduction (P less than 0.01). The terminal elimination rate constant (beta) was 0.27 +/- 0.16 h-1 for the control session and 0.14 +/- 0.069 h-1 with propranolol (P less than 0.05); terminal elimination half-lives were 2.6 and 4.9 h, respectively. Volume of distribution was unchanged. Because bupivacaine clearance should be relatively insensitive to hepatic perfusion, it appeared that propranolol caused a substantial inhibition of bupivacaine metabolism at the level of the hepatocyte. These data suggest that concomitant use of propranolol could result in the accumulation of a toxic concentration of bupivacaine.