Placental transfer of tofacitinib in the ex vivo dual-side human placenta perfusion model.

Autor:	Eliesen GAM; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, the Netherlands.; Centre for Safety of Substances and Products, National Institute for Public Health and the Environment, Bilthoven, the Netherlands., Fransen M; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, the Netherlands., van Hove H; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, the Netherlands., van den Broek PHH; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, the Netherlands., Greupink R; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, the Netherlands.
Jazyk:	angličtina
Zdroj:	Current research in toxicology [Curr Res Toxicol] 2024 Jan 08; Vol. 6, pp. 100149. Date of Electronic Publication: 2024 Jan 08 (Print Publication: 2024).
DOI:	10.1016/j.crtox.2024.100149
Abstrakt:	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 ex vivo 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 ex vivo perfused placenta tofacitinib traverses the placental barrier rapidly and extensively. This suggests that substantial fetal tofacitinib exposure will take place after maternal drug dosing. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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