Embryo-fetal distribution of a biopharmaceutical IgG2 during rat organogenesis

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 300 mg/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.

► Plasma IgG2 fetal:maternal ratio decreased with increasing dose at end of gestation.
► Plasma IgG2 fetal:maternal ratio increased with increasing days since last dose.
► IgG2 present in rat embryonic tissue increased >100-fold between gestation day 10 and 17.
► IgG2 present in rat embryonic tissue demonstrate potential for direct toxicity.