Morphine bioavailability from a topical gel formulation in volunteers.
Morphine bioavailability from a topical gel formulation in volunteers.
复制标题
志愿者中局部凝胶制剂的吗啡生物利用度。
DOI：
10.1016/j.jpainsymman.2007.04.016
复制
发表时间：
2008
影响因子：
4.7
通讯作者：
Avram,MichaelJ
中科院分区：
文献类型：
--
作者：
Paice,JudithA;VonRoenn,JamieH;Hudgins,JCraig;Luong,Lynn;Krejcie,TomC;Avram,MichaelJ
虽然现有的治疗方法可以缓解许多癌症相关疼痛的患者，但吞咽困难或肠梗阻可能会使一些患者无法口服止痛剂。局部吗啡可能提供另一种给药形式，但局部凝胶制剂的吗啡生物利用度尚未在人类中报道。我们对五名志愿者进行了随机、安慰剂对照、双盲、交叉研究，他们提供了机构批准的书面知情同意书。他们两次进入西北大学综合临床研究中心，随机分配第一次接受1mL以10mg/mL复配的pluronic卵磷脂有机凝胶（PLO）碱涂在手腕上并皮下给予1mL生理盐水，第一次接受1mL外用无药PLO碱加1mL 3mg/mL皮下吗啡，第二次接受相反的组合。在给药后5min ~ 10h采集17份血样进行吗啡浓度测定。血浆样品采用固相萃取法制备，吗啡浓度采用质谱法测定，线性范围为0.5 ~ 500ng/mL。局部制剂相对于皮下剂量的生物利用度是通过剂量和血浆吗啡浓度与时间的关系来估计的。由于局部给药后血浆样品中很少检出吗啡，且检出时无法定量，故局部吗啡的低生物利用度无法定量。这些结果表明，局部给药吗啡复合在一个PLO基础上经皮给药不太可能提供缓解癌症相关的疼痛。
Although available therapies provide relief to many patients with cancer-related pain, swallowing difficulties or intestinal obstruction may preclude oral analgesic delivery in some. Topical morphine might provide an alternate delivery form but morphine bioavailability from a topical gel formulation has not been reported in humans. We conducted a randomized, placebo-controlled, double-blind, crossover study of five volunteers after they provided institutionally-approved, written, informed consent. They were admitted to the Northwestern University General Clinical Research Center twice, being randomly assigned to receive either 1mL of morphine compounded at 10mg/mL in pluronic lecithin organogel (PLO) base applied to the wrist and 1mL of normal saline administered subcutaneously, or 1mL of topical drug-free PLO base and 1mL of subcutaneous morphine, 3mg/mL, the first time and the opposite combination the second. Seventeen blood samples were collected from 5minutes to 10hours after dose administration for morphine concentration determination. Plasma samples were prepared by solid-phase extraction and morphine concentrations measured by a mass spectrometric technique with a linear range of 0.5–500ng/mL. Bioavailability of the topical formulation relative to the subcutaneous dose was to be estimated from doses and the plasma morphine concentration versus time relationships. Because morphine was seldom detected in plasma samples after topical administration and was unquantifiable when it was, the low bioavailability of topical morphine was unquantifiable. These results suggest that topical administration of morphine compounded in a PLO base for transdermal drug delivery is unlikely to provide relief of cancer-related pain.