Pharmacokinetics of naloxone: an insight into the locus of effect on stress-ulceration.
Pharmacokinetics of naloxone: an insight into the locus of effect on stress-ulceration.
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纳洛酮的药代动力学：深入了解应激性溃疡的作用部位。
DOI：
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发表时间：
1989
影响因子：
3.5
通讯作者：
K. Ephgrave
中科院分区：
文献类型：
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作者：
R. Kleiman;C. G. Adair;K. Ephgrave
本研究的目的是通过测量大鼠在4小时的约束应激期间的纳洛酮血药浓度，确定纳洛酮对急性胃粘膜病变形成的有益作用是通过中枢机制还是外周机制实现的。该研究涉及给大鼠施用5、20和40毫克/千克-1剂量的纳洛酮。Hr通过静脉或肠内途径。在整个克制期间采集血液样本，并在实验结束时统计胃应激损伤。两种给药途径在预防应激性溃疡方面同样有效，只有静脉注射药物的大鼠血液样本中显示出纳洛酮的存在。平均谷血浓度与病变呈反线性关系（P = 0.0003），时间-浓度曲线下面积与平均谷血浓度呈线性相关（P = 0.0001）。虽然我们的研究结果显示，静脉给药组的血液水平与对病变的影响密切相关，但这种影响一定是对外周而不是中枢阿片受体的影响，因为当静脉给药时，没有发现可检测到的血液水平。
The purpose of this study was to determine if the beneficial effect of naloxone on formation of acute gastric mucosal lesions was brought about via central or peripheral mechanisms by measuring blood concentrations of naloxone in rats during a 4-hr period of restraint stress. The study involved administration of naloxone to rats at doses of 5, 20 and 40 mg.kg-1.hr by either the intravenous or enteral routes. Blood samples were collected throughout the period of restraint and gastric stress-lesions were counted at the end of the experiments. Both routes of administration were equally effective in preventing stress-ulceration, with only rats receiving drug intravenously showing the presence of naloxone in blood samples. Inverse linear relationships existed between mean trough blood concentrations and lesions (P = .0003), as well as a linear correlation between area under the time-concentration curve and mean trough concentrations (P = .0001). Although our results show tight correlation between blood levels and effect on lesions in the group given drug intravenously, the effect must be on peripheral rather than central opiate receptors as no detectable blood levels were found when naloxone was given enterally.