Ternant David, Ducourau Emilie, Perdriger Aleth, Corondan Anca, Le Goff Benoît, Devauchelle-Pensec Valérie, Solau-Gervais Elisabeth, Watier Hervé, Goupille Philippe, Paintaud Gilles, Mulleman Denis
Université François Rabelais de Tours, GICC, Tours, France; CNRS, UMR 7293, Tours, France; CHRU de Tours, Tours, France.
Br J Clin Pharmacol. 2014 Jul;78(1):118-28. doi: 10.1111/bcp.12313.
Infliximab, an anti-tumour necrosis factor-α monoclonal antibody, is indicated in rheumatoid arthritis (RA). Our objective was to evaluate the influence of the sources of infliximab pharmacokinetic variability in RA.
Eighty-four patients treated with infliximab for RA were included in a prospective noncomparative study. They were analysed between two consecutive infliximab infusions. Infliximab concentrations were measured before the infusion, 2 h, 1 and 4 weeks after the infusion and immediately before the next infusion. Infliximab concentrations were described using a two-compartment population pharmacokinetic model.
The mean (interindividual standard deviation) estimated central volume of distribution was 2.3 l (36%) and systemic clearance was 0.019 l h(-1) (37%). The central volume of distribution increased with bodyweight; it was doubled between 50 and 90 kg. Systemic clearance increased with pre-infusion C-reactive protein concentration by 20%, varying from 3 to 14 mg l(-) 1, and was decreased by 30% when methotrexate was coadministered.
The influence of methotrexate and inflammation on infliximab clearance suggests that individual adjustment of infliximab doses according to disease activity may be useful in RA.
英夫利昔单抗是一种抗肿瘤坏死因子-α单克隆抗体，用于治疗类风湿关节炎（RA）。我们的目的是评估类风湿关节炎中英夫利昔单抗药代动力学变异性来源的影响。
84例接受英夫利昔单抗治疗的类风湿关节炎患者纳入一项前瞻性非对照研究。在两次连续输注英夫利昔单抗期间对他们进行分析。在输注前、输注后2小时、1周和4周以及下次输注前即刻测量英夫利昔单抗浓度。使用二室群体药代动力学模型描述英夫利昔单抗浓度。
估计的平均（个体间标准差）中央分布容积为2.3升（36%），全身清除率为0.019升/小时（37%）。中央分布容积随体重增加；在50至90千克之间增加了一倍。全身清除率随输注前C反应蛋白浓度增加20%，C反应蛋白浓度范围为3至14毫克/升，当联合使用甲氨蝶呤时全身清除率降低30%。
甲氨蝶呤和炎症对英夫利昔单抗清除率的影响表明，根据疾病活动度对英夫利昔单抗剂量进行个体化调整在类风湿关节炎中可能有用。
