title: Embryo-fetal distribution of a biopharmaceutical IgG2 during rat organogenesis.
abstract: Embryo-fetal biodistribution of a maternally administered humanized IgG2 in rats was evaluated by enzyme-linked immunosorbent assay in dose response and time course studies. Fetal and maternal plasma IgG2 levels increased with dose from 10 to 300mg/kg but fetal:maternal ratio decreased with increasing dose. Plasma IgG2 levels decreased in fetal rat with increasing time post-dose but more slowly than maternal levels. This difference in post-dose kinetics resulted in an increased fetal:maternal ratio with increasing days since last dose. Lastly, IgG2 in embryo-fetal tissue was detected at very low levels on gestation day (GD) 10-12 and levels increased over 100-fold by GD 17. The profile of increasing IgG2 levels as gestation progressed continued in extra-embryonic fluid (GD 12-19) until the end of gestation in fetal plasma (GD 19-21). Based on the current study, there is a potential for direct effects on rat embryo-fetal development following maternal administration of a biopharmaceutical IgG2.
authors.affiliation: Drug Safety Research & Development, Pfizer Worldwide Research & Development, Groton, CT 06340, United States. christopher.j.bowman@pfizer.com
authors.forename: C J
authors.initials: CJ
authors.lastname: Bowman
authors.forename: L E
authors.initials: LE
authors.lastname: King
authors.forename: D B
authors.initials: DB
authors.lastname: Stedman
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood / Q000493:pharmacokinetics*; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology*; D008431:Maternal-Fetal Exchange; D038081:Organogenesis / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G