Nishio Shinichiro, Yamamoto Tatsuhiro, Kaneko Kaichi, Tanaka-Matsumoto Nahoko, Muraoka Sei, Kaburaki Makoto, Kusunoki Yoshie, Takagi Kenji, Kawai Shinichi
Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Ota-ku, Tokyo, Japan.
Mod Rheumatol. 2009;19(3):329-33. doi: 10.1007/s10165-009-0158-0. Epub 2009 Mar 3.
The main aim of this study is to investigate the pharmacokinetics of infliximab and Fcgamma receptor (FcgammaR) polymorphism in two patients with rheumatoid arthritis (RA) who were well controlled by low-dose infliximab. A 57-year-old woman (Patient 1) and a 67-year-old woman (Patient 2) had active RA despite methotrexate and prednisolone treatments. They improved after the addition of infliximab (3 mg/kg), but developed pneumonia and sepsis, respectively. Although the infliximab doses were reduced to 1.5 mg/kg and 1 mg/kg, respectively, clinical improvements were maintained. Blood samples were obtained at 1 h after infliximab administration and at eight weeks (just before the next dose). The elimination half-life was determined by the serum concentration of infliximab. We also analyzed the polymorphisms of FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB for the genomic DNA samples from the two patients and three controls. Amplification of the FcgammaR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. Decresed clearance of infliximab was proven by a pharmacokinetic study of these patients under low-dose infliximab therapy. 131H/H (FcgammaRIIA) and 176F/F (FcgammaRIIIA) were detected in both patients. NA1/NA2 and NA2/NA2 (FcgammaRIIIB) were detected in Patients 1 and 2, respectively. These patients were well controlled over the long term by low-dose infliximab. The mechanism of the reduced clearance of infliximab might possibly be explained in part by the FcgammaR polymorphisms.
本研究的主要目的是调查两名类风湿关节炎（RA）患者在低剂量英夫利昔单抗控制良好的情况下英夫利昔单抗的药代动力学及Fcγ受体（FcγR）多态性。一名57岁女性（患者1）和一名67岁女性（患者2）尽管接受了甲氨蝶呤和泼尼松龙治疗，但仍患有活动性RA。加用英夫利昔单抗（3mg/kg）后病情改善，但分别出现了肺炎和败血症。尽管英夫利昔单抗剂量分别降至1.5mg/kg和1mg/kg，但临床改善得以维持。在英夫利昔单抗给药后1小时和八周（下次给药前）采集血样。通过英夫利昔单抗的血清浓度确定消除半衰期。我们还分析了两名患者和三名对照的基因组DNA样本中FcγRIIA、FcγRIIIA和FcγRIIIB的多态性。采用同种异型特异性聚合酶链反应扩增FcγR基因组区域以区分基因型。通过对这些患者在低剂量英夫利昔单抗治疗下的药代动力学研究，证实了英夫利昔单抗清除率降低。两名患者均检测到131H/H（FcγRIIA）和176F/F（FcγRIIIA）。患者1和患者2分别检测到NA1/NA2和NA2/NA2（FcγRIIIB）。这些患者通过低剂量英夫利昔单抗长期得到良好控制。英夫利昔单抗清除率降低的机制可能部分由FcγR多态性解释。
