佐剂诱导性关节炎大鼠体内吗啡的药代动力学
Pharmacokinetics of Morphine in Rats with Adjuvant-induced Arthritis.
作者信息
Kimura Yoshiaki, Shibata Mika, Tamada Mika, Ozaki Noriyuki, Arai Kunizo
机构信息
Faculty of Pharmacy, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan.
Suisen Pharmacy, Fukui Pharmaceutical Association, Eiheiji, Japan.
出版信息
In Vivo. 2017 Sep-Oct;31(5):811-817. doi: 10.21873/invivo.11134.
We investigated the in vivo dynamics and analgesic effect of morphine using an adjuvant-induced arthritis (AA) rat as a model of chronic inflammation. Morphine generally binds to μ-opioid receptors in the brain to exert its effects. After several minutes, it is metabolized by glucuronidation via a UDP-glucuronosyltransferase (UGT). Here, we showed that in AA rats, UGT activity in liver microsomes was reduced. Morphine-free serum fractions in AA rats were also decreased (control, 84.9%; AA, 63.9%) and the expression of ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1), which plays a crucial role in morphine bile excretion, decreased to 23.0% that of the control group. However, we observed no significant difference between the AA and control groups regarding blood concentrations of morphine and morphine-3-glucuronide. In contrast, the analgesic effect of morphine increased 4-fold in AA rats. Our results showed that the pharmacokinetics of morphine is not changed, but the pharmacodynamics of morphine is enhanced in chronic inflammation.
我们以佐剂诱导的关节炎（AA）大鼠作为慢性炎症模型，研究了吗啡的体内动力学和镇痛效果。吗啡通常与大脑中的μ-阿片受体结合以发挥其作用。几分钟后，它通过UDP-葡萄糖醛酸基转移酶（UGT）经葡萄糖醛酸化作用进行代谢。在此，我们表明在AA大鼠中，肝微粒体中的UGT活性降低。AA大鼠中无吗啡血清分数也降低（对照组为84.9%；AA组为63.9%），且在吗啡胆汁排泄中起关键作用的ATP结合盒转运体B亚家族（MDR/TAP）成员1（ABCB1）的表达降至对照组的23.0%。然而，我们观察到AA组和对照组在吗啡和吗啡-3-葡萄糖醛酸的血药浓度方面无显著差异。相反，吗啡在AA大鼠中的镇痛效果增加了4倍。我们的结果表明，吗啡的药代动力学未改变，但在慢性炎症中吗啡的药效学增强。
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