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阿片类药物药代动力学的性别差异。

Gender-related differences in the pharmacokinetics of opiates.

机构信息

Institute of Forensic Medicine, Clinical Center Vojvodina, Novi Sad, Serbia.

出版信息

Forensic Sci Int. 2010 Jan 30;194(1-3):28-33. doi: 10.1016/j.forsciint.2009.10.003. Epub 2009 Nov 12.

DOI:10.1016/j.forsciint.2009.10.003
PMID:19913374
Abstract

Previous studies have documented gender-related differences in a number of aspects of the pharmacology of opiates, including their analgesic activity, stimulative properties and generation of physical dependence. The current experiments were carried out with the aim to examine whether male-female differences exist in the blood and brain levels of opiates attained after their intraperitoneal injection to male and female Wistar rats. The tests were performed 5, 15, 45 and 120 min after the animal treatment with seized heroin. Gas chromatography-mass spectrometry (GC-MS) method was developed to quantitatively determine opiate alkaloids in blood and brain regions (known for their high concentration of mu-opiate receptors): cortex, brainstem, amygdala and basal ganglia. Maximal contents of opiates in blood of animals of both genders were found in the second measurement time (15 min), the values measured in the males being significantly higher, which suggests a faster passage of the opiates from blood to brain tissue in female animals. The highest content of opiates in the brain tissue of female animals was measured 15 min and with male animals 45 min after the treatment, which also indicates faster distribution of opiates from blood to brain in the female compared to male rats. The highest proportion of opiates was found in the basal ganglia of the animals of both genders. The obtained results offer the possibility of selecting this part of the brain tissue of both males and females as a representative sample for identifying and assessing contents of opiates.

摘要

先前的研究已经记录了阿片类药物药理学在许多方面存在性别差异,包括其镇痛活性、刺激性和身体依赖性的产生。目前的实验旨在检查雄性和雌性 Wistar 大鼠腹腔注射后,其血液和大脑中阿片类药物的水平是否存在性别差异。在动物接受海洛因后 5、15、45 和 120 分钟进行了测试。建立了气相色谱-质谱(GC-MS)方法来定量测定血液和大脑区域(已知其含有高浓度的 mu 阿片受体)中的阿片类生物碱:皮质、脑干、杏仁核和基底神经节。在两性动物的第二次测量时间(15 分钟)中发现了血液中阿片类药物的最大含量,男性的测量值明显更高,这表明阿片类药物在雌性动物中更快地从血液转移到脑组织。雌性动物脑组织中阿片类药物的最高含量在治疗后 15 分钟和雄性动物 45 分钟时测量到,这也表明阿片类药物在雌性动物中的血液向大脑的分布速度比雄性更快。阿片类药物在两性动物的基底神经节中含量最高。所获得的结果提供了选择两性动物的该脑组织部分作为识别和评估阿片类药物含量的代表性样本的可能性。

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