title: Pharmacokinetic study and Fcgamma receptor gene analysis in two patients with rheumatoid arthritis controlled by low-dose infliximab.
abstract: 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.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Ota-ku, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nishio
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kaichi
authors.initials: K
authors.lastname: Kaneko
authors.forename: Nahoko
authors.initials: N
authors.lastname: Tanaka-Matsumoto
authors.forename: Sei
authors.initials: S
authors.lastname: Muraoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Kaburaki
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Kusunoki
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kawai
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D000069285:Infliximab; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C496124:FCGR3A protein, human; C428200:FCGR3B protein, human; C080568:Fc gamma receptor IIA; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; D000069285:Infliximab