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Influence of stress on pharmacokinetics of various drugs

应激对多种药物药代动力学的影响

基本信息

批准号：
02671053
负责人：
GOMITA Yutaka
金额：
$ 1.22万
依托单位：
Okayama University Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

In the present study, influences of emotinal stress on pharmacokinetics of various therapeutic drugs such as nicorandil, isosorbide dinitrate, vasodilators with nitrate, and tlieophylline, bronchodilator, were investigated in male Wistar rats. Restilts obtained were as follows ;(A)Influence of footshock stress on pharmacokinetics of nicorandil --- In the group exposed to footshock(30 min)after the oral administration of nicorandil(10 mg/kg), plasma nicorandil levels were markedly lower than those in the control group. Plasma levels after the subcutaneous injection(5 mg/kg)were also slightly but significantly lower in stressed rats than in control rats. Furthermore, footshock applied immediately after intravenous injection of nicorandil(3 mg/kg)significantly decreased the plasma levels. Nicorandil levels in the heart, kidney, and skin were significantly lowel, in th e stressed rats, but levels in the muscle, liver and tliymus showed no difference. The urinary excretion of nicorandil ten … More ded to be higher in the stressed rats. These results suggest that footshock stress affectsnot only tlie absorption of nicorandil but also its distribution, metabolism and excretion.(B)Influence of footshock stress on Pharmacokinetics of isosorbide dinitrate--- The plasma level of isosorbide dinitrate intraperitoneally adiministered to rats stressed by footsliock was almost the same as that in the control rats. However, levels of its metabolites, 5-isosorbide mononitrate and 2- isosorbide mononitrate, were lower in stressed rats than in the control rats, suggestidg that footsliock stress may idfluence the metabolism and/or excretion of the metabolites.(C)Influences of various emotional stresses on pharmacokinetics of theophylline--- In the group exposed to footsliock(30-60 min)after oral administration of theophylline(20 mg/kg), plasma theophylline levels were significantly lower than those in the control rats. Futhermore in the group immobilized by mesh wire(30-60 min)after the drug administration. the plasma levels were also markedly lower.These results suggest that emotional stress such as footshock and immobilization afffects pliarmacokinetics of various therapeutic drugs such as nicorandil, isosorbide dinitrate and theophylline. Less

在本研究中，在雄性Wistar大鼠中研究了情绪应激对各种治疗药物（如尼可地尔、硝酸异山梨酯、硝酸盐血管扩张剂和茶碱、支气管扩张剂）药代动力学的影响。获得的结果如下：（A）足电击应激对尼可地尔药代动力学的影响-在尼可地尔（10 mg/kg）经口给药后暴露于足电击（30 min）的组中，血浆尼可地尔水平显著低于对照组。皮下注射（5 mg/kg）后，应激大鼠的血浆水平也略低于对照大鼠，但显著低于对照大鼠。此外，静脉注射尼可地尔（3 mg/kg）后立即进行足电击可显著降低血浆水平。应激大鼠心脏、肾脏和皮肤中的尼可地尔水平显著降低，但肌肉、肝脏和关节中的尼可地尔水平无差异。尼可地尔10的尿排泄 ...更多信息在应激大鼠中，提示足电击应激不仅影响尼可地尔的吸收，而且影响其分布、代谢和排泄。（B）足电击应激对硝酸异山梨酯药代动力学的影响--足电击应激大鼠腹腔注射硝酸异山梨酯后血浆中硝酸异山梨酯浓度与对照组基本相同。但应激大鼠的代谢产物5-单硝酸异山梨酯和2-单硝酸异山梨酯的水平低于对照组，提示足滑应激可能影响代谢产物的代谢和/或排泄。（C）各种情绪应激对茶碱药代动力学的影响-在口服茶碱（20 mg/kg）后暴露于足垫（30-60 min）的组中，血浆茶碱水平显著低于对照大鼠。网状钢丝固定组于给药后30-60 min给予氟替卡松。血浆水平也明显较低。这些结果表明，足部电击和制动等情绪应激会影响尼可地尔、硝酸异山梨酯和茶碱等多种治疗药物的动力学。少