title: Population pharmacokinetic evaluation of a fully human IgG monoclonal antibody in patients with inflammatory diseases.
abstract: ABX-IL8 is a fully human IgG₂ monoclonal antibody generated using transgenic mouse technology (Xenomouse®) that binds to human Interleukin-8 with high affinity and specificity. The objective of this study was to evaluate the pharmacokinetic (PK) properties of ABX-IL8 in patients with active inflammatory diseases. Patients with psoriasis and rheumatoid arthritis received single or multiple short intravenous infusions of ABX-IL8 or placebo. Serum concentrations of ABX-IL8, baseline serum IgG and IgG₂ concentrations and Anti-Drug Antibody (ADA) response to ABX-IL8 were determined using relevant immunoassays. Pharmacokinetic analyses of the serum ABX-IL8 concentration-time data were performed. Following single-dose administration of ABX-IL8, dose proportional increases in drug exposure were observed. Consistent with the disposition properties of the endogenous IgG antibodies, ABX-IL8 appeared to be primarily distributed into the plasma compartment and the extra-vascular fluid and the steady-sate volume of distribution (61 ± 14 to 71 ± 14 mL/kg) was comparable to that for the endogenous antibodies. Following the multiple-dose administration, PK properties of the antibody were linear with dose and time. Steady-state clearance (2.6 ± 1.1 to 2.7 ± 1.4 mL/day/kg) was similar to that observed following the single dose administration and no ADA response was detected throughout the study. PK variability and serum exposure to ABX-IL8 following administration of the fixed doses were comparable to those observed following administration of the weight-adjusted doses; the impact of body weight on clearance was minimal and this correlation did not translate into requirements for body weight-adjusted dosing. Additionally, age and disease type (psoriasis or RA) had no impact on ABX-IL8 pharmacokinetics.
authors.affiliation: Amgen (Fremont) Inc., 6701 Kaiser Drive, Fremont, CA 94556, USA. mtabrizi@anaptysBio.com
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tabrizi
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Saling
authors.initials: S
authors.lastname: Huang
authors.forename: Gregory
authors.initials: G
authors.lastname: Bell
authors.forename: Gisela
authors.initials: G
authors.lastname: Schwab
authors.forename: Lorin
authors.initials: L
authors.lastname: Roskos
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: C492798:ABX-Interleukin 8; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents