Marginal transfer of ReoPro™ (Abciximab) compared with immunoglobulin G (F105), inulin and water in the perfused human placenta in vitro

被引:33
作者
Miller, RK
Mace, K
Polliotti, B
DeRita, R
Hall, W
Treacy, G
机构
[1] Univ Rochester, Med Ctr, Dept Obstet & Gynecol, Rochester, NY 14642 USA
[2] Univ Rochester, Med Ctr, Dept Environm Med, Rochester, NY 14642 USA
[3] Univ Rochester, Med Ctr, Environm Hlth Sci Ctr, Rochester, NY 14642 USA
[4] Centocor Inc, Pharmaceut Res, Malvern, PA 19355 USA
[5] A Charles River Co, Frederick, MD USA
关键词
D O I
10.1016/S0143-4004(03)00101-2
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
ReoPro(TM) (Abciximab), a Fab fragment of a human-murine chimeric monoclonal antibody, binds to glycoprotcin IIb/IIla 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. RcoPro, along with (H2O)-H-3, inulin or I-125-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 mug/ml). (H2O)-H-3 rapidly appeared in the fetal circuit, while fetal C-14-inulin never equilibrated with the maternal inulin. After 6 h, I-125-F105 was present with fetal/maternal percentagcs-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.
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页码:727 / 738
页数:12
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