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101.
柑橘类果汁对大鼠细胞色素P450 3A的抑制与果汁中呋喃香豆素组成的相关性 总被引:3,自引:0,他引:3
目的:呋喃香豆素类(补骨脂素类)是导致葡萄柚汁与药物相互作用的重要成分。本研究拟调查该类化合物在其它柑橘类果汁中的存在,并比较这些果汁对细胞色素P450(CYP)3A活性的抑制强度。方法:用梯度高压液相色谱法测定柑橘类的鲜榨果汁中6种呋喃香豆素化合物的组成与含量。以雄性Sprague-Dawley大鼠肝微粒体的睾酮613.羟化活性测试每种果汁对CYP3A的抑制作用。结果:与葡萄柚汁比较,Jaffa sweetie果汁中呋喃香豆素的组成与含量基本相同,对CYP3A的抑制强度也相当;日本红柚、溪蜜柚和金柚的果汁中呋喃香豆素组成相似但含量较低,对CYP3A的抑制强度也较弱;常山胡柚、甜橙与宽皮橘果汁中呋喃香豆素种类少且含量极低。且多数对CYP3A无抑制作用。结论:根据呋喃香豆素组成可以预测柑橘类果汁因为抑制CYP3A引起的药物相互作用;琯溪蜜柚及近缘品种的果汁可能导致类似于葡萄柚汁的药物相互作用,有必要在临床上加以验证。 相似文献
102.
细胞色素P450与药物代谢的研究现状 总被引:15,自引:8,他引:15
细胞色素P450(CYP)在众多中西药物代谢中起着非常重要的作用。本文综述了与药物代谢相关的CYP亚型、CYP与药物相互作用的关系及中药对CYP的影响,旨在合理解释和预测临床上药物间相互作用和药物不良反应等。同时选择适当的药物作为探针来评价CYP的活性,为实现临床个体化给药提供科学依据。 相似文献
103.
Naphthalene (NA) is metabolized to highly reactive intermediates that are primarily detoxified by conjugation to glutathione (GSH). Intraperitoneal administration of naphthalene causes substantial loss of both hepatic and respiratory GSH, yet only respiratory tissues are injured in mice. The liver supplies GSH to other organs via the circulation, making it unclear whether respiratory GSH losses reflect in situ respiratory depletion or decreased hepatic supply. To address this concern, mice were exposed to naphthalene by inhalation (1.5-15 ppm; 2-4 h), thereby bypassing first-pass hepatic involvement. GSH levels and histopathology were monitored during the first 24 h after exposure. Half of the mice were given the GSH depletor diethylmaleate (DEM) 1 hour before naphthalene exposure. Lung and nasal GSH levels rapidly decreased (50-90%) in mice exposed to 15 ppm naphthalene, with cell necrosis throughout the respiratory tract becoming evident several hours later. Conversely, 1.5 ppm naphthalene caused moderate GSH loss and only injured the nasal olfactory epithelium. Neither naphthalene concentration depleted hepatic GSH. Animals pretreated with DEM showed significant GSH loss and injury in nasal and intrapulmonary airway epithelium at both naphthalene concentrations. DEM treatment, perhaps by causing significant GSH loss, decreased water-soluble naphthalene metabolite formation by 48% yet increased NA-protein adducts 193%. We conclude that (1) GSH depletion occurs in airways independent of hepatic function; (2) sufficient GSH is not supplied by the liver to maintain respiratory GSH pools, or to prevent injury from inhaled naphthalene; and (3) GSH loss precedes injury and increases protein adduct formation. 相似文献
104.
《Drug metabolism reviews》2012,44(1-2):89-116
Dehydroepiandrosterone has been thought to have physiological functions other than as an androgen precursor. The previous studies performed have demonstrated a number of biological effects in rodents, such as amelioration of disease in diabetic, chemical carcinogenesis, and obesity models. To date, activation of the peroxisome proliferators activated receptor alpha, pregnane X receptor, and estrogen receptor by DHEA and its metabolites have been demonstrated. Several membrane-associated receptors have also been elucidated leading to additional mechanisms by which DHEA may exert its biological effects. This review will provide an overview of the receptor multiplicity involved in the biological activity of this sterol. 相似文献
105.
106.
《Drug metabolism reviews》2012,44(2-3):515-538
The microsomal cytochrome P450 (CYP) family 4 monooxygenases are the major fatty acid ω-hydroxylases. These enzymes remove excess free fatty acids to prevent lipotoxicity, catabolize leukotrienes and prostanoids, and also produce bioactive metabolites from arachidonic acid ω-hydroxylation. In addition to endogenous substrates, recent evidence indicates that CYP4 monooxygenases can also metabolize xenobiotics, including therapeutic drugs. This review focuses on human CYP4 enzymes and updates current knowledge concerning catalytic activity profiles, genetic variation and regulation of expression. Comparative differences between the human and rodent CYP4 enzymes regarding catalytic function and conditional expression are also discussed. 相似文献
107.
The field of mechanistic chemical carcinogenesis has evolved with the advent and advances in genomic, proteomic and metabolomic technologies. These advances allow mechanistic events along the process of exposure to frank tumors to be studied in great detail. Herein is reviewed an example of this approach using, propiconazole, a triazole-containing antifungal agent that is a mouse hepatocarcinogen. This review will highlight those toxicological, genomic, proteomic and metabolomic findings in mice that were used to describe a set of linked events that lead to propiconazole-induced hepatocarcinogenesis. Independent experimental proof of many of these events is presented that solidified this proposed mechanism of carcinogenic action for propiconazole. 相似文献
108.
Yogeshkumar Nanasaheb Gavhane Adhikrao Vyankatrao Yadav 《Saudi Pharmaceutical Journal》2012,20(4):331-344
The aim of this review is to provide a broad perspective on intestinal absorption and the impact of intestinal first-pass metabolism on both clearance and drug–drug interaction prediction along with its historical perspectives. The review also considers abilities to bridge the gap between the increasing amount of intestinal in vitro data and the importance of intestinal first-pass metabolism in vivo. The significance of efflux transporters on the intestinal absorption is also discussed. 相似文献
109.
110.
Santosh Kumar Sreevatsav Adiraju Kiran Shekar John F. Fraser Maree T. Smith 《Drug metabolism reviews》2018,50(2):109-124
For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities of cytochrome P450 (CYP) isoenzymes. PK changes during cardiac surgery with CPB have the potential to adversely affect the safety and efficacy of pharmacotherapy and increase the risk of drug–drug interactions. Clinically significant changes in drug PK during CPB are likely to be prominent for drugs where CYP metabolism is a major clearance (CL) mechanism. However, clinical data from patients undergoing CPB surgery in support of this hypothesis are lacking, leaving a significant knowledge gap. In this review, we address the effects of CPB on the release of pro-inflammatory cytokines, in surgeries with and without CPB, both pre and post initiation of surgery. We reviewed literature to explore the relationship between the release of pro-inflammatory cytokines, and the expression and activities of CYP enzymes. Through this approach, we provide new insight on the effects of CPB on the PK of drugs administered to patients in the clinical setting. Future research to address this knowledge gap will have considerable impact to assist clinicians with optimizing pharmacotherapy in this patient population. 相似文献