Westin Ulrika Espefält, Boström Emma, Gråsjö Johan, Hammarlund-Udenaes Margareta, Björk Erik
Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23, Uppsala, Sweden.
Pharm Res. 2006 Mar;23(3):565-72. doi: 10.1007/s11095-006-9534-z. Epub 2006 Feb 25.
The aim of this study was to quantify the olfactory transfer of morphine to the brain hemispheres by comparing brain tissue and plasma morphine levels after nasal administration with those after intravenous administration.
Morphine (1.0 mg/kg body weight) was administered via the right nostril or intravenously as a 15-min constant-rate infusion to male rats. The content of morphine and its metabolite morphine-3-glucuronide in samples of the olfactory bulbs, brain hemispheres, and plasma was assessed using high-performance liquid chromatography, and the areas under the concentration-time curves (AUC) were calculated.
At both 5 and 15 min after administration, brain hemisphere morphine concentrations after nasal administration were similar to those after i.v. administration of the same dose, despite lower plasma concentrations after nasal administration. The brain hemispheres/plasma morphine AUC ratios for the 0-5 min period were thus approximately 3 and 0.1 after nasal and i.v. administration, respectively, demonstrating a statistically significant early distribution advantage of morphine to the brain hemispheres via the nasal route.
Morphine is transferred via olfactory pathways to the brain hemispheres, and drug transfer via this route significantly contributes to the early high brain concentrations after nasal administration to rats.
本研究的目的是通过比较经鼻给药后与静脉给药后脑组织和血浆中的吗啡水平，来量化吗啡向脑半球的嗅觉转运。
将吗啡（1.0毫克/千克体重）以15分钟恒速输注的方式经右鼻孔或静脉注射给雄性大鼠。使用高效液相色谱法评估嗅球、脑半球和血浆样本中吗啡及其代谢产物吗啡-3-葡萄糖醛酸苷的含量，并计算浓度-时间曲线下面积（AUC）。
给药后5分钟和15分钟时，尽管经鼻给药后的血浆浓度较低，但经鼻给药后脑半球的吗啡浓度与静脉注射相同剂量后的浓度相似。因此，0至5分钟期间经鼻给药和静脉给药的脑半球/血浆吗啡AUC比值分别约为3和0.1，表明经鼻途径给药后吗啡向脑半球的早期分布具有统计学显著优势。
吗啡通过嗅觉途径转运至脑半球，经此途径的药物转运对大鼠经鼻给药后早期脑内高浓度有显著贡献。
