The Pharmacokinetics and Pharmacodynamics of Liposome Bupivacaine Administered Via a Single Epidural Injection to Healthy Volunteers
The Pharmacokinetics and Pharmacodynamics of Liposome Bupivacaine Administered Via a Single Epidural Injection to Healthy Volunteers
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DOI：
10.1097/aap.0b013e318269d29e
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发表时间：
2012-11-01
影响因子：
5.1
通讯作者：
Ludbrook, Guy L.
中科院分区：
文献类型：
--
作者：
Viscusi, Eugene R.;Candiotti, Keith A.;Ludbrook, Guy L.
背景和目的：本研究的目的是在健康志愿者中评估硬膜外给药脂质体布比卡因与盐酸布比卡因的药代动力学、感觉/运动效应和安全性。方法：30名受试者随机接受脂质体布比卡因89、155或266 mg，或盐酸布比卡因50 mg双盲治疗。运动阻断的发生/持续时间、针刺/冷敏感性和布比卡因血浆水平在给药96小时后进行评估。对耐受性参数也进行了评估。结果：所有剂量的布比卡因脂质体均比50mg盐酸布比卡因曲线下面积更大，最大血浆浓度和终末消除半衰期观察时间更长。布比卡因脂质体的平均最大血药浓度为89和155 mg（但不是266 mg），显著低于盐酸布比卡因50 mg （P < 0.001）。脂质体布比卡因266mg运动阻断的中位持续时间为1小时，盐酸布比卡因为2.8小时。在接受脂质体布比卡因266mg的受试者中，29%（2/7）在给药后4小时无法行走，而接受盐酸布比卡因的受试者中有67%（4/6）无法行走。脂质体布比卡因266 mg组针刺/冷敏感性损失的中位持续时间分别为36和69小时，而盐酸布比卡因组针刺和冷敏感性损失的中位持续时间均为12小时。脂质体布比卡因耐受性良好；所有治疗组中最常见的不良事件是注射部位疼痛，大多数受试者在30天内消退。结论：硬膜外给药脂质体布比卡因266 mg比脂质体布比卡因89或155 mg或盐酸布比卡因50 mg的感觉阻滞持续时间更长。脂质体布比卡因266 mg与盐酸布比卡因相比，运动阻断持续时间更短。
Background and Objectives: The objective of this study was to assess the pharmacokinetics, sensory/motor effects, and safety of epidurally administered liposome bupivacaine versus bupivacaine HCl in healthy volunteers.Methods: Thirty subjects were randomized to receive liposome bupivacaine 89, 155, or 266 mg, or bupivacaine HCl 50 mg in a double-blind fashion. Occurrence/duration of motor blockade, pinprick/cold sensitivity, and plasma bupivacaine levels were assessed for 96 hours after study drug administration. Tolerability parameters were also assessed.Results: All doses of liposome bupivacaine resulted in greater area under the curve and a longer time to observed maximum plasma concentration and terminal elimination half-life than bupivacaine HCl 50 mg. Mean maximum plasma concentration with liposome bupivacaine 89 and 155 mg (but not 266 mg) was statistically significantly lower than with bupivacaine HCl 50 mg (P < 0.001). Median duration of motor blockade with liposome bupivacaine 266 mg was 1 hour versus 2.8 hours for bupivacaine HCl. Of subjects who received liposome bupivacaine 266 mg, 29% (2/7) were unable to ambulate at 4 hours postdose versus 67% (4/6) of those receiving bupivacaine HCl. Median durations of pinprick/cold sensitivity loss were 36 and 69 hours, respectively, in the liposome bupivacaine 266-mg group versus 12 hours for both pinprick and cold in the bupivacaine HCl group. Liposome bupivacaine was well tolerated; the most common adverse event in all treatment groups was injection site pain, which resolved within 30 days for most subjects.Conclusions: Epidurally administered liposome bupivacaine 266 mg resulted in a longer duration of sensory blockade than liposome bupivacaine 89 or 155 mg or bupivacaine HCl 50 mg. Duration of motor blockade was shorter with liposome bupivacaine 266 mg versus bupivacaine HCl.