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Placental disposition of eculizumab, C5 and C5‐eculizumab in two pregnancies of a woman with paroxysmal nocturnal haemoglobinuria
Author(s) -
Eliesen Gaby A.M.,
Drongelen Joris,
Broek Petra H.H.,
Sarlea Andrei,
Heijden Olivier W.H.,
Langemeijer Saskia,
Greupink Rick,
Volokhina Elena B.,
Russel Frans G.M.
Publication year - 2021
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14565
Subject(s) - eculizumab , placenta , pregnancy , medicine , cord , cord blood , fetus , immunology , surgery , antibody , complement system , biology , genetics
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.