Placental disposition of eculizumab, C5 and C5-eculizumab in two pregnancies of a woman with paroxysmal nocturnal haemoglobinuria
SourceBritish Journal of Clinical Pharmacology, 87, 4, (2021), pp. 2128-2131
Article / Letter to editor
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IMM - Institute for Molecules and Materials
British Journal of Clinical Pharmacology
SubjectRadboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 16: Vascular damage RIHS: Radboud Institute for Health Sciences; Radboudumc 2: Cancer development and immune defence RIHS: Radboud Institute for Health Sciences; Radboudumc 5: Inflammatory diseases RIMLS: Radboud Institute for Molecular Life Sciences
Eculizumab is known to cross the placenta to a limited degree, but recently therapeutic drug levels in cord blood were found in a single case. We report maternal, cord and placental levels of unbound eculizumab, C5 and C5-eculizumab in two pregnancies of a paroxysmal nocturnal haemoglobinuria patient who received 900 mg eculizumab every 2 weeks. In both pregnancies, cord blood concentrations of unbound eculizumab were below 4 μg/mL, while C5-eculizumab levels were 22 and 26 μg/mL, suggesting that a considerable fraction of C5 was blocked in the newborn. Concentrations in each placenta of unbound eculizumab were 41 ± 3 and 45 ± 4 μg/g tissue, of C5-eculizumab 19 ± 2 and 32 ± 3 μg/g, and of C5 20 ± 3 and 30 ± 2 μg/g (mean ± SD, in three tissue samples per placenta). Placental levels of unbound eculizumab were higher than those of C5-eculizumab complexes, while maternal concentrations were approximately equal, suggesting selective transport of unbound eculizumab across the placenta.
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