Zhou Honghui
Clinical Pharmacology, Wyeth Pharmaceuticals, Collegeville, PA 19426, USA.
J Clin Pharmacol. 2005 May;45(5):490-7. doi: 10.1177/0091270004273321.
Etanercept, a fully humanized soluble recombinant tumor necrosis factor receptor fusion protein, is an approved treatment for rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis. Etanercept is absorbed slowly from the site of subcutaneous injection, with time to peak concentration at approximately 48 to 60 hours, and is cleared slowly from the body with a t(1/2) of 70 to 100 hours. The absolute bioavailability of etanercept was 58% in healthy subjects following subcutaneous administration. The 25-mg twice-weekly dosage regimen generates systemic exposures comparable to 50 mg once weekly, as predicted by pharmacokinetic modeling and simulation and later confirmed by clinical studies. The pharmacokinetics of etanercept in patients with rheumatoid arthritis are comparable to those in healthy individuals and patients with ankylosing spondylitis, congestive heart failure, and psoriasis. In children with polyarticular-course juvenile rheumatoid arthritis, after subcutaneous doses of 0.4 mg/kg twice weekly, the clearance of etanercept may be slightly reduced in children aged 4 to 8 years. Pharmacokinetic simulation predicts that a dose of 0.8 mg/kg once weekly generates comparable systemic exposure as 0.4 mg/kg twice weekly. No requirement for etanercept dosage adjustment is needed when etanercept is coadministered with warfarin, digoxin, or methotrexate.
依那西普是一种完全人源化的可溶性重组肿瘤坏死因子受体融合蛋白，是一种已获批准用于治疗类风湿性关节炎、幼年类风湿性关节炎、银屑病关节炎、强直性脊柱炎和银屑病的药物。依那西普从皮下注射部位吸收缓慢，达峰浓度时间约为48至60小时，从体内清除缓慢，半衰期为70至100小时。皮下给药后，健康受试者中依那西普的绝对生物利用度为58%。如药代动力学建模和模拟所预测并随后经临床研究证实，每周两次25毫克的给药方案产生的全身暴露量与每周一次50毫克相当。类风湿性关节炎患者中依那西普的药代动力学与健康个体以及强直性脊柱炎、充血性心力衰竭和银屑病患者中的药代动力学相当。在多关节型幼年类风湿性关节炎患儿中，每周两次皮下注射0.4毫克/千克后，4至8岁儿童中依那西普的清除率可能会略有降低。药代动力学模拟预测，每周一次0.8毫克/千克的剂量产生的全身暴露量与每周两次0.4毫克/千克相当。依那西普与华法林、地高辛或甲氨蝶呤合用时，无需调整依那西普剂量。
