PHARMACOKINETICS AND PHARMACODYNAMICS OF MORPHINE-3-GLUCURONIDE IN RATS AND ITS INFLUENCE ON THE ANTINOCICEPTIVE EFFECT OF MORPHINE
PHARMACOKINETICS AND PHARMACODYNAMICS OF MORPHINE-3-GLUCURONIDE IN RATS AND ITS INFLUENCE ON THE ANTINOCICEPTIVE EFFECT OF MORPHINE
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DOI：
10.1002/bdd.2510140102
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发表时间：
1993-01-01
影响因子：
2.1
通讯作者：
HAMMARLUNDUDENAES, M
中科院分区：
文献类型：
--
作者：
EKBLOM, M;GARDMARK, M;HAMMARLUNDUDENAES, M
在本研究中，研究了大鼠静脉推注（86.7 mumol kg-1）和恒速输注（2.9 mumol h-1）5天后吗啡-3-葡糖苷酸（M3 G）的药代动力学和药效学。推注给药后，清除率（Cl）为12.1 +/- 0.6 ml min-1*kg，稳态分布容积（V（ss））为1.68 +/- 0.89 l kg-1，第一相半衰期为13.2 +/- 1.8 min，第二相半衰期为11.6 +/- 7.7 h。恒速输注后，Cl为10.5 +/- 1.7 ml min-1*kg。在第4天M3 G稳态浓度期间和M3 G幼稚大鼠中，测试了M3 G对单次剂量吗啡（35 μ mol kg-1）的抗伤害效应的拮抗作用。M3 G给药后未观察到镇痛、痛觉过敏或戒断作用，但与对照组相比，M3 G输注组吗啡的镇痛作用显著降低。全身给药M3 G拮抗吗啡的抗伤害性作用，但这不是唯一的解释吗啡给药后观察到的耐受性发展。
In this study the pharmacokinetics and pharmacodynamics of morphine-3-glucuronide (M3G) were investigated in rats after i.v. administration as a bolus dose (86.7 mumol kg-1) and as a constant rate infusion (2.9 mumol h-1) over 5 days. After the bolus dose, the clearance (Cl) was 12.1 +/- 0.6 ml min-1*kg, the volume of distribution at steady state (V(ss)) 1.68 +/- 0.89 l kg-1, the half-life of the first phase 13.2 +/- 1.8 min and the half-life of the second phase 11.6 +/- 7.7 h. After the constant rate infusion, Cl was 10.5 +/- 1.7 ml min-1*kg. The antagonistic effect of M3G on the antinociceptive effect of a bolus dose of morphine (35 mumol kg-1) was tested during steady state concentrations of M3G on day 4 and to M3G naive rats. No antinociceptive, hyperalgesic or withdrawal effects were observed as a result of M3G administration, but a significantly lower antinociceptive effect of morphine was found in the M3G infusion group compared to the control group. Systemically administered M3G antagonized the antinociceptive effect of morphine, but this cannot be the only explanation to the tolerance development observed after morphine administration.