Xenobiotic transfer of onabotulinumtoxinA using an ex vivo human placental perfusion model: A pilot study

OnabotulinumtoxinA is an effective preventive therapy for chronic migraine; however, data on fetal exposure during pregnancy are limited. We aimed to evaluate transplacental transfer of onabotulinumtoxinA using an ex vivo human placental perfusion model.

Five term placentas from uncomplicated singleton pregnancies were cannulated and perfused using a validated ex vivo model. OnabotulinumtoxinA (100 units in Trials 1 and 2; 200 units in Trials 3-5) was introduced into the maternal circuit with antipyrine (1 g/L) as a positive transfer control. Maternal and fetal samples were collected every 30 min for 3 h. Fetal artery pressure and pH were monitored to ensure system integrity. Antipyrine was measured using ultra-high performance liquid chromatography-mass spectrometry, and onabotulinumtoxinA using enzyme-linked immunosorbent assay.

OnabotulinumtoxinA was not detected in fetal samples at any time point. Antipyrine demonstrated expected transplacental transfer, confirming model validity. Maternal onabotulinumtoxinA concentrations decreased slightly over time.

OnabotulinumtoxinA was not detected in the fetal circulation under study conditions, suggesting minimal transplacental transfer. These preliminary findings support its potential use in pregnancy; however, in vivo studies are needed to confirm maternal-fetal pharmacokinetics.