Udeani G O, Bass J, Johnston T P
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago 60612.
Ann Pharmacother. 1994 Apr;28(4):451-5. doi: 10.1177/106002809402800404.
Patients with terminal cancer often receive continuous enteral nutrition and oral medications concomitantly through nasogastric or gastrostomy feeding tubes. This study evaluated in vitro the compatibility of morphine sulfate (MS) solution 2 mg/mL (Roxane Laboratories) with three enteral nutrition products (Jevity [J], Osmolite-HN [O], and Pulmocare [P]) at 22 and 37 degrees C for 48 hours and J alone at 50 degrees C for 48 hours.
Mixtures containing 1 mg/mL MS were prepared with each enteral product: J, O, and P (Ross Laboratories). Serial samples (1 mL) were collected from each mixture and analyzed for morphine by reverse-phase HPLC. An analog pH meter was used to measure the pH of each mixture at scheduled intervals.
The addition of MS 2 mg/mL (MS2) to J caused an immediate decrease in pH from 6.24 +/- 0.01 to 4.96 +/- 0.05 and a noticeable precipitate/phase separation. No phase separation was observed with a 1 mg/mL mixture of MS and J, O, and P when they were prepared with a more concentrated MS solution (20 mg/mL, MS20) (Roxanol Intensol). The pH declined linearly for all three enteral feeding products as the MS20 concentration was increased from 0 to 1 mg/mL. The precipitate observed in the mixture of MS2 with J was probably caused by the decrease in pH, which was caused by the greater volume fraction of MS solution. The concentration of morphine in the supernatant of a MS2/J solution was 0.83 mg/mL, and the concentration of MS in a homogeneous MS20/J solution was 0.86 mg/mL. At 48 hours, there was negligible (< 2 percent) morphine decomposition in all MS admixtures at all temperatures. No microbial growth was observed in any admixture at 24 hours. Electrophoretic analysis demonstrated equal protein migration and molecular weight distribution for J and MS/J solutions.
MS is stable in enteral feeding solutions at temperatures from 22 to 50 degrees C. MS2 is associated with a pH-dependent protein precipitation (but not destruction of the proteins), resulting in disproportionate concentrations of morphine in the supernatant and precipitate. This incompatibility may adversely affect enteral feeding analgesic delivery. We, therefore, recommend MS 20 mg/mL for this method of oral MS delivery, because of its superior compatibility and stability with enteral feeding products.
晚期癌症患者常通过鼻胃管或胃造口喂养管同时接受持续肠内营养和口服药物治疗。本研究在体外评估了2mg/mL硫酸吗啡（MS）溶液（Roxane实验室）与三种肠内营养产品（能全力[J]、奥米力特-HN[O]和百普力[P]）在22℃和37℃下48小时的相容性，以及单独的能全力在50℃下48小时的相容性。
用每种肠内产品（罗斯实验室的J、O和P）制备含1mg/mL MS的混合物。从每种混合物中收集系列样品（1mL），并用反相高效液相色谱法分析吗啡。使用模拟pH计按预定时间间隔测量每种混合物的pH值。
向能全力中添加2mg/mL MS（MS2）导致pH值立即从6.24±0.01降至4.96±0.05，并出现明显的沉淀/相分离。当用更浓缩的MS溶液（20mg/mL，MS20）（Roxanol Intensol）制备MS与能全力、奥米力特-HN和百普力的1mg/mL混合物时，未观察到相分离。随着MS20浓度从0增加到1mg/mL，所有三种肠内喂养产品的pH值呈线性下降。MS2与能全力混合物中观察到的沉淀可能是由于pH值降低所致，而pH值降低是由MS溶液的更大体积分数引起的。MS2/能全力溶液上清液中吗啡的浓度为0.83mg/mL，均匀的MS20/能全力溶液中MS的浓度为0.86mg/mL。在48小时时，所有温度下所有MS混合物中的吗啡分解可忽略不计（<2%）。在24小时时，任何混合物中均未观察到微生物生长。电泳分析表明，能全力和MS/能全力溶液的蛋白质迁移和分子量分布相同。
MS在22至50℃的肠内喂养溶液中稳定。MS2与pH值依赖性蛋白质沉淀有关（但蛋白质未被破坏），导致上清液和沉淀中吗啡浓度不成比例。这种不相容性可能会对肠内喂养镇痛药物的递送产生不利影响。因此，由于其与肠内喂养产品具有更好的相容性和稳定性，我们推荐使用20mg/mL的MS用于这种口服MS给药方法。
