The Pharmacokinetics and Pharmacodynamics of Bupivacaine-Loaded Microspheres on a Brachial Plexus Block Model in Sheep
The Pharmacokinetics and Pharmacodynamics of Bupivacaine-Loaded Microspheres on a Brachial Plexus Block Model in Sheep
复制标题
布比卡因微球在绵羊臂丛神经阻滞模型上的药代动力学和药效学
DOI：
10.1213/00000539-200108000-00042
复制
发表时间：
2001
影响因子：
5.7
通讯作者：
C. Ecoffey
中科院分区：
文献类型：
--
作者：
J. Estebe;P. Le Corre;Laure Du Plessis;F. Chevanne;G. Cathelineau;R. Le Verge;C. Ecoffey
我们使用绵羊臂丛阻滞模型评估布比卡因微球（B-Ms）。第一步，对75 mg盐酸布比卡因（B-HCl）（静脉输注和臂丛阻滞）进行药代动力学表征（n = 12）。第二步，对37.5 mg、75 mg、150 mg、300 mg和750 mg的B-HCl进行臂丛阻滞剂量反应研究。作为比较，使用750毫克布比卡因碱(B)进行评估。第三步，采用B- ms (750 mg B作为B- ms)，采用60/40和50/50 （w/w %）两种配方，对臂丛阻滞进行评估；同时对无毒微球进行了评价。在静脉给药B-HCl （750 mg和300 mg）、B-Ms （750 mg）和无药微球（30 mL / 1 min）后进行毒性评估。随着B-HCl剂量的增加，以布比卡因血浆浓度的增加为代价，阻滞的开始时间缩短，完全运动阻断的持续时间延长。最大浓度时间似乎与B-HCl剂量无关。在臂丛阻滞中，37.5 mg剂量的B-HCl不会引起运动阻滞，而750 mg剂量的B-HCl在临床上是有毒的。在静脉给药的情况下，剂量为300毫克的B-HCl与750毫克的B-HCl毒性相同。与75 mg B- hcl给药相比，750 mg B- hcl作为B- ms给药增加了完全运动阻断的持续时间，但最大浓度无显著差异。两种B-Ms制剂的临床差异无统计学意义。静脉给药B-Ms是安全的。结论：微球控释布比卡因可延长臂丛神经阻滞时间，且无明显毒性。
We evaluated bupivacaine-loaded microspheres (B-Ms) using a brachial plexus block model in sheep. In the first step, pharmacokinetic characterization of 75 mg bupivacaine hydrochloride (B-HCl) (IV infusion and brachial plexus block) was performed (n = 12). In the second step, a brachial plexus block dose response study of B-HCl was performed with 37.5 mg, 75 mg, 150 mg, 300 mg, and 750 mg. As a comparison, evaluations were performed using a 750-mg bupivacaine base (B). In the third step, evaluations of brachial plexus block were performed with B-Ms (750 mg of B as B-Ms) using two formulations, 60/40 and 50/50 (w/w %); drug-free microspheres were also evaluated. Toxicity evaluations were also performed after IV administration of B-HCl (750 mg and 300 mg), B-Ms (750 mg), and drug-free microspheres (30 mL over 1 min). As the B-HCl dose increased, the time of onset of block decreased and the duration of complete motor blockade increased at the expense of an increase in bupivacaine plasma concentrations. The time of maximum concentration appeared to be independent of the B-HCl dose. In brachial plexus block, a 37.5-mg dose of B-HCl did not induce motor blockade whereas a dose of 750 mg of B-HCl was clinically toxic. In the case of IV administration, doses of 300 mg of B-HCl were as toxic as 750 mg of B-HCl. Compared with the 75 mg of B-HCl administration for brachial plexus block, administration of 750 mg of B as B-Ms increased the duration of complete motor blockade without significant difference in maximum concentration. No significant clinical difference between the two formulations of B-Ms was demonstrated. The IV administration of B-Ms was safe. We conclude that the controlled release of bupivacaine from microspheres prolonged the brachial plexus block without obvious toxicity.