Pharmacokinetics of murine p75-Fc fusion protein and MP6-XT22 anti-murine TNF-alpha mAb in mice.
Immunologic limitations make it difficult to study the pharmacokinetic effects of human tumor necrosis factor (TNF) blockers in murine models. To counter this, we have studied the pharmacokinetics in mice of two murine analogs of human TNF blockers, a murine p75-FC fusion protein (analogous to etanercept), and the rat MP6-XT22 anti-murine TNF mAb (analogous to infliximab). We analyzed the pharmacokinetics of the murine p75-Fc protein and MP6-XT22 antibody in mice that were uninfected and in mice with disseminated candidiasis in order to confirm dosing strategies and interpret future studies evaluating the efficacy and tolerability of these agents in mice. We propose that, while conducting safety or efficacy studies in murine disease models, it is reasonable to administer the murine p75-Fc protein to mice at <10 mg/kg every 4-5 days, and the MP6-XT22 antibody at 10-20 mg/kg every 4-5 days.
Filler
Scott G
SG
Department of Medicine, Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA. sfiller@ucla.edu
Solis
Norma V
NV
Guo
Jane
J
Doellgast
George
G
Ruiz-Garcia
Ana
A
Pan
Wei-Jian
WJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics*; D002177:Candidiasis / Q000276:immunology; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D000069285:Infliximab; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D011993:Recombinant Fusion Proteins / Q000097:blood / Q000493:pharmacokinetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept