Marginal transfer of ReoPro (Abciximab) compared with immunoglobulin G (F105), inulin and water in the perfused human placenta in vitro.
ReoPro (Abciximab), a Fab fragment of a human-murine chimeric monoclonal antibody, binds to glycoprotein IIb/IIIa receptors on human platelets and inhibits platelet aggregation. Can ReoPro transit the human placenta since it does not have an Fc (domain) as does IgG? This question was addressed using an in vitro term human placental lobular dual perfusion model. ReoPro, along with 3H(2)O, inulin or 125I-F105 human IgG(1), were added to the maternal reservoir for 6 or >12 h, ReoPro was equivalent to, or exceeded, clinically relevant plasma concentrations (0.3-3 microg/ml). 3H(2)O rapidly appeared in the fetal circuit, while fetal 14C-inulin never equilibrated with the maternal inulin. After 6 h, 125I-F105 was present with fetal/maternal percentages-0.55 per cent. ReoPro was not detectable (<3.9 ng/ml) in the fetal circuit during or at the end of any perfusion. Using immunohistochemistry, ReoPro was only detected attached to maternal and fetal platelets, and to the trophoblastic surface of the placental villi. Only pharmaceutically insignificant amounts of ReoPro were detected in the fetal circuit, which demonstrates a barrier capacity of the human term placenta for this Fab fragment compared with IgG.
Miller
R K
RK
Department of Obstetrics and Gynecology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642-8668, USA. richardk_miller@urmc.rochester.edu
Mace
K
K
Polliotti
B
B
DeRita
R
R
Hall
W
W
Treacy
G
G
D000077284:Abciximab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D001692:Biological Transport; D001792:Blood Platelets / Q000378:metabolism; D002824:Chorionic Villi / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G / Q000378:metabolism*; D007444:Inulin / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D008431:Maternal-Fetal Exchange; D009924:Organ Culture Techniques; D010477:Perfusion; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D014316:Tritium; D014867:Water / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D014867:Water; D014316:Tritium; D007444:Inulin; D000077284:Abciximab