蛋白酶抑制剂在艾滋病患者。临床上重要的药代动力学因素。
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Barry M,长臂猿,D,玛尔卡茜F
蛋白酶抑制剂在艾滋病患者。临床上重要的药代动力学因素。
Pharmacokinet。1997年3月,32 (3):194 - 209。
- PubMed ID
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9084959 (在PubMed]
- 文摘
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自1987年推出以来,齐多夫定单药治疗HIV感染患者的治疗选择。不幸的是,它建立了齐多夫定的有益影响不是由于持续发展耐药病毒株。这导致联合治疗的策略,并于1995年与齐多夫定治疗+必要,或叠氮胸苷+ zalcitabine,被证明是更有效的比齐多夫定单一疗法在预防疾病进展,减少艾滋病患者的死亡率。最近的研究表明一个更大的抗病毒效应从三联疗法2核苷,齐多夫定+ zalcitabine saquinavir添加,一个新的蛋白酶抑制剂药物。HIV蛋白酶酶负责插科打诨的翻译后加工和gag pol多蛋白前体,及其抑制saquinavir等药物,例如indinavir和vx - 478结果生产非传染性病毒粒子。当电阻也可以开发的蛋白酶抑制剂可以用于组合,和未来的战略很可能包括四2与核苷(酸)类似物治疗+ 2蛋白酶抑制剂。管理蛋白酶抑制剂单独或与其他药物确实提出一些重要的艾滋病患者的药代动力学问题。一些蛋白酶抑制剂(如saquinavir)动力学资料的特点是减少吸收和高第一轮效应,导致可怜的生物利用度可能提高管理与食物。生理因素包括胃酸缺乏症、吸收不良和肝功能障碍可能影响蛋白酶抑制剂在艾滋病毒疾病的生物利用度。蛋白酶抑制剂是高度与血浆蛋白(> 98%),主要为α1-acid糖蛋白。 This may influence their antiviral activity in vitro and may also predispose to plasma protein displacement interactions. Such interactions are usually only of clinical relevance if the metabolism of the displaced drug is also inhibited. This is precisely the situation likely to pertain to the protease inhibitors, as ritonavir may displace other protease inhibitor drugs, such as saquinavir, from plasma proteins and inhibit their metabolism. Protease inhibitors are extensively metabolised by the cytochrome P450 (CYP) enzymes present in the liver and small intestine. In vitro studies suggest that the most influential CYP isoenzyme involved in the metabolism of the protease inhibitors is CYP3A, with the isoforms CYP2C9 and CYP2D6 also contributing. Ritonavir has an elimination half-life (t1/2 beta) of 3 hours, indinavir 2 hours and saquinavir between 7 and 12 hours. Renal elimination is not significant, with less than 5% of ritonavir and saquinavir excreted in the unchanged form. As patients with HIV disease are likely to be taking multiple prolonged drug regimens this may lead to drug interactions as a result of enzyme induction or inhibition. Recognised enzyme inducers of CYP3A, which are likely to be prescribed for patients with HIV disease, include rifampicin (rifampin) [treatment of pulmonary tuberculosis], rifabutin (treatment and prophylaxis of Mycobacterium avium complex), phenobarbital (phenobarbitone), phenytoin and carbamazepine (treatment of seizures secondary to cerebral toxoplasmosis or cerebral lymphoma). These drugs may reduce the plasma concentrations of the protease inhibitors and reduce their antiviral efficacy. If coadministered drugs are substrates for a common CYP enzyme, the elimination of one or both drugs may be impaired. Drugs which are metabolised by CYP3A and are likely to be used in the treatment of patients with HIV disease include the azole antifungals, macrolide antibiotics and dapsone; therefore, protease inhibitors may interact with these drugs. (ABSTRACT TRUNCATED)
beplay体育安全吗DrugBank数据引用了这篇文章
- 药物靶点
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药物 目标 类 生物 药理作用 行动 齐多夫定 逆转录酶/ RNaseH 蛋白质 人类免疫缺陷病毒1 是的抑制剂细节 - 药物的相互作用Learn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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药物 交互 整合药物之间
在您的软件的交互Amprenavir 卡马西平 时可以降低血清浓度Amprenavir结合卡马西平。 Asunaprevir 卡马西平 时可以降低血清浓度Asunaprevir结合卡马西平。 Atazanavir 卡马西平 时可以降低血清浓度Atazanavir结合卡马西平。 Fosamprenavir 卡马西平 时可以降低血清浓度Fosamprenavir结合卡马西平。 Indinavir 卡马西平 时可以降低血清浓度Indinavir结合卡马西平。 奈非那韦 卡马西平 奈非那韦的血清浓度时可以减少与卡马西平相结合。 Saquinavir 卡马西平 时可以降低血清浓度Saquinavir结合卡马西平。 Tipranavir 卡马西平 时可以降低血清浓度Tipranavir结合卡马西平。
