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Pharmacokinetics and Safety of Golimumab, a Fully Human Anti‐TNF‐α Monoclonal Antibody, in Subjects With Rheumatoid Arthritis
Author(s) -
Zhou Honghui,
Jang Haishan,
Fleischmann Roy M.,
BoumanThio Esther,
Xu Zhenhua,
Marini Joseph C.,
Pendley Charles,
Jiao Qun,
Shankar Gopi,
Marciniak Stanley J.,
Cohen Stanley B.,
Rahman Mahboob U.,
Baker Daniel,
Mascelli Mary Ann,
Davis Hugh M.,
Everitt Daniel E.
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006298188
Subject(s) - golimumab , pharmacokinetics , volume of distribution , medicine , population , nonmem , rheumatoid arthritis , pharmacology , bioequivalence , etanercept , environmental health
Golimumab is a fully human antitumor necrosis factor alpha (TNF‐α) monoclonal antibody that is being developed for intravenous and subcutaneous administration. To assess the pharmacokinetics and safety of the intravenous formulation of golimumab, 36 adult subjects with rheumatoid arthritis were randomly assigned to receive a single infusion of placebo or golimumab (0.1, 0.3, 1, 3, 6, or 10 mg/kg). Serum concentrations of golimumab were determined using a validated enzyme‐linked immunosorbent assay method. In addition to the noncompartmental analysis and compartmental modeling, a population pharmacokinetics analysis using NONMEM was also conducted. Both the maximum serum concentration and the area under the serum concentration‐time curve appeared to increase in a dose‐proportional manner. The median half‐life ranged from 7 to 20 days. A 2‐compartment population pharmacokinetic model adequately described the pharmacokinetics of golimumab. The following pharmacokinetic parameters (typical value [% coefficient of variation]) were estimated from the population pharmacokinetic model: clearance (CL: 0.40 [10.1%] L/d), volume of distribution in the central compartment (V c : 3.07 [6.4%] L), intercompartmental clearance (Q: 0.42 [15.5%] L/d), and volume of distribution in the peripheral compartment (V p : 3.68 [11.8%] L). Interindividual variability of the pharmacokinetic parameters was quantified for CL (44.3%), V c (25.5%), Q (44.6%), and V p (44.6%). Residual variability was estimated to be 15.0%. Body weight was found to be an important covariate on V c . Golimumab was generally well tolerated. The pharmacokinetics of golimumab appeared to be linear over the dose range evaluated in this study.