Barjavel M, Sandouk P, Plotkine M, Scherrmann J M
INSERM Unité 26, Hôpital Fernand Widal, Paris.
Life Sci. 1994;55(16):1301-8. doi: 10.1016/0024-3205(94)90069-8.
Morphine (M), morphine 3-glucuronide (M3G) and morphine 6-glucuronide (M6G) were subcutaneously administered at 10 mg/kg in three groups of six awake rats. A transverse microdialysis probe was implanted in the brain cortex and dialysates were collected every 30 minutes for a period of 4 hours. Dialysates were measured by two different opiate radioimmunoassays. Maximum brain opiate concentrations, 41 +/- 10 ng/ml (M), 147 +/- 27 ng/ml (M3G), 177 +/- 43 ng/ml (M6G), were reached at the same Tmax, 0.75 h, and elimination half-lives ranged from 0.99 to 0.81 h for the 3 compounds. Kinetic parameters confirmed that penetration and elimination rates in the extracellular space of the rat brain cortex for the 2 hydrophilic M metabolites were similar to those of M. These results indicate for the first time that, in spite of their structural differences, glucuronide metabolites of M are capable of crossing the blood-brain-barrier (BBB) at the same rate as morphine does, but in higher amount.
将三组每组六只清醒大鼠分别皮下注射10毫克/千克的吗啡（M）、吗啡3-葡萄糖醛酸苷（M3G）和吗啡6-葡萄糖醛酸苷（M6G）。在大脑皮层植入横向微透析探针，每30分钟收集一次透析液，共收集4小时。通过两种不同的阿片类放射免疫测定法对透析液进行检测。三种化合物在相同的达峰时间（Tmax）0.75小时达到最大脑阿片类药物浓度，分别为41±10纳克/毫升（M）、147±27纳克/毫升（M3G）、177±43纳克/毫升（M6G），消除半衰期在0.99至0.81小时之间。动力学参数证实，两种亲水性M代谢物在大鼠大脑皮层细胞外空间的渗透和消除速率与M相似。这些结果首次表明，尽管M的葡萄糖醛酸苷代谢物结构不同，但它们能够以与吗啡相同的速率穿过血脑屏障（BBB），但量更大。
