临床药物动力学和使用英夫利昔单抗。
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克洛茨U, Teml,施瓦布M
临床药物动力学和使用英夫利昔单抗。
Pharmacokinet。2007; 46 (8): 645 - 60。doi: 10.2165 / 00003088-200746080-00002。
- PubMed ID
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17655372 (在PubMed]
- 文摘
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肿瘤坏死因子-α(TNFalpha)是一种重要的促炎细胞因子参与了慢性炎症性疾病。英夫利昔单抗,嵌合(human-murine)单克隆IgG1 anti-TNFalpha抗体,用于治疗克罗恩病(包括fistulising疾病)和类风湿关节炎(结合甲氨蝶呤)如果标准治疗失败了。英夫利昔单抗的迹象已经扩大到包括强直性脊柱炎、银屑病关节炎、牛皮癣和溃疡性结肠炎。英夫利昔单抗生物代理是由多个静脉注入剂量的3 - 5毫克/公斤(最初在周0、2和6;随后在4 - 8周的时间间隔)。在对照试验中,20 - 40%的临床反应率取得了这样的方案在克罗恩氏病和风湿性关节炎。然而,疗效必须平衡各种严重不良事件的风险(如严重感染包括肺结核、肝毒性、输液反应,血清sickness-like疾病和淋巴瘤)。英夫利昔单抗的单个和多个输液后,没有发现相关的差异值浓度时间配置文件之间的克罗恩病的患者,类风湿性关节炎患者和患者牛皮癣。高分子量的表观分布容积英夫利昔单抗(149.1 kDa)低(3-6L)和代表了血管内空间。长期坚持在这个舱(消除半衰期7 - 12天,平均停留时间12 - 17天)是由于非常低的系统性间隙约为11至15毫升/小时(0.18 - -0.25毫升/分钟)。beplayapp Elimination of infliximab is most probably accomplished through degradation by unspecific proteases. During multiple infusions (every 4-8 weeks), no accumulation was observed, and serum concentrations and the area under the plasma concentration-time curve of infliximab increased in proportion to the infused dose, indicating linear pharmacokinetics. Co-medication with methotrexate delayed the decline in the serum concentrations of infliximab. When relating serum concentrations to the clinical response in patients with rheumatoid arthritis and patients with Crohn's disease, it can be assumed that trough concentrations above 1 microg/mL could be used as a kind of therapeutic target. In the future, identification of biomarkers for (non-)response and risk factors for adverse drug reactions would be very helpful. Furthermore, combined biological, pharmacokinetic, pharmacogenomic and clinical studies have not yet been performed and are needed to optimise the therapeutic potential of infliximab, which is currently established as a rescue treatment in refractory patients.
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- 药物