阿托伐他汀的临床药物动力学。
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Lennernas H
阿托伐他汀的临床药物动力学。
Pharmacokinet。2003; 42 (13): 1141 - 60。
- PubMed ID
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14531725 (在PubMed]
- 文摘
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鸡蛋是一个风险因素对动脉粥样硬化疾病的发展。阿托伐他汀能降低血浆低密度脂蛋白(LDL)胆固醇水平β-还原酶的抑制作用。平均剂量反应关系已被证明是对数线性阿托伐他汀,但等离子体浓度的阿托伐他汀酸及其代谢产物不与低密度脂蛋白胆固醇降低在给定的剂量。阿托伐他汀的临床剂量范围为10 - 80毫克/天,并给出它的酸的形式。阿托伐他汀酸是高度可溶和渗透,药物口服后吸收完全。然而,阿托伐他汀酸受到广泛的肠道壁以及初步的新陈代谢在肝脏,作为口服生物利用度为14%。阿托伐他汀酸分布的体积是381 l,和血浆蛋白结合超过98%。阿托伐他汀酸是广泛在肠道和肝脏的氧化新陈代谢lactonisation glucuronidation,代谢物是消除胆汁分泌和直接从血肠道分泌。在体外,阿托伐他汀酸是22的衬底,有机anion-transporting多肽(OATP) C和H +元羧酸酸转运蛋白。阿托伐他汀酸的总等离子体间隙是625毫升/分钟,半衰期约为7个小时。 The renal route is of minor importance (<1%) for the elimination of atorvastatin acid. In vivo, cytochrome P450 (CYP) 3A4 is responsible for the formation of two active metabolites from the acid and the lactone forms of atorvastatin. Atorvastatin acid and its metabolites undergo glucuronidation mediated by uridinediphosphoglucuronyltransferases 1A1 and 1A3. Atorvastatin can be given either in the morning or in the evening. Food decreases the absorption rate of atorvastatin acid after oral administration, as indicated by decreased peak concentration and increased time to peak concentration. Women appear to have a slightly lower plasma exposure to atorvastatin for a given dose. Atorvastatin is subject to metabolism by CYP3A4 and cellular membrane transport by OATP C and P-glycoprotein, and drug-drug interactions with potent inhibitors of these systems, such as itraconazole, nelfinavir, ritonavir, cyclosporin, fibrates, erythromycin and grapefruit juice, have been demonstrated. An interaction with gemfibrozil seems to be mediated by inhibition of glucuronidation. A few case studies have reported rhabdomyolysis when the pharmacokinetics of atorvastatin have been affected by interacting drugs. Atorvastatin increases the bioavailability of digoxin, most probably by inhibition of P-glycoprotein, but does not affect the pharmacokinetics of ritonavir, nelfinavir or terfenadine.
DrugBank数据引用了这篇文章
- 药物
- 药物酶
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药物 酶 类 生物 药理作用 行动 阿托伐他汀 UDP-glucuronosyltransferase 1 - 1 蛋白质 人类 没有底物细节 阿托伐他汀 UDP-glucuronosyltransferase 1 - 3 蛋白质 人类 没有底物细节 - 药物转运蛋白
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药物 转运体 类 生物 药理作用 行动 阿托伐他汀 22 - 1 蛋白质 人类 没有底物抑制剂细节 阿托伐他汀 溶质载体有机阴离子转运蛋白家族成员1 b1 蛋白质 人类 没有底物抑制剂细节 阿托伐他汀 溶质载体有机阴离子转运蛋白家族成员1 b3 蛋白质 人类 没有底物细节 - 药物反应
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反应 细节 细节 细节 细节 细节 - 药物的相互作用Learn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
