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Placental transfer of tofacitinib in the dual-side human placenta perfusion model. | LitMetric

AI Article Synopsis

  • * Researchers performed experiments using human placental tissue to study how much tofacitinib crosses the placental barrier, and found that drug levels were similar in both maternal and fetal sides after perfusion.
  • * The study indicates that tofacitinib transfers quickly and extensively through the placenta, suggesting that unborn babies could be significantly exposed to the drug when mothers take it.

Article Abstract

Tofacitinib is a small molecule Janus kinase (JAK) inhibitor, introduced to the European market in 2017, for the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. In the treatment of women with autoimmune diseases, pregnancy is a relevant issue, as such diseases typically affect women in their reproductive years. Currently, there is limited data on the use of tofacitinib during pregnancy. To estimate the extent of placental transfer in the absence of clinical data, we conducted dual-side perfused human placental cotyledon perfusions. Term placentas were perfused for 180 min with tofacitinib (100 nM, added to the maternal circuit) in a closed-closed configuration. At the end of the perfusions, drug concentrations in the maternal and fetal reservoirs were near equilibrium, at 35.6 ± 5.5 and 24.8 ± 4.7 nM, respectively. Transfer of tofacitinib was similar to that observed for the passive diffusion marker antipyrine (100 µg/mL, added to the maternal reservoir). Final antipyrine maternal and fetal concentrations amounted to 36.9 ± 3.0 and 36.7 ± 1.3 µg/mL, respectively. In conclusion, in the perfused placenta tofacitinib traverses the placental barrier rapidly and extensively. This suggests that substantial fetal tofacitinib exposure will take place after maternal drug dosing.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10825226PMC
http://dx.doi.org/10.1016/j.crtox.2024.100149DOI Listing

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