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

Objective: 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. Study design: 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. Results: 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. Conclusion: 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.