Placental disposition of the immunosuppressive drug tacrolimus in renal transplant recipients and in ex vivo perfused placental tissue

• Published in: European journal of pharmaceutical sciences 2018-07, Vol.119, p.244-248
• Main Authors: Freriksen, J.J.M., Feyaerts, D., van den Broek, P.H.H., van der Heijden, O.W.H., van Drongelen, J., van Hamersvelt, H.W., Russel, F.G.M., van der Molen, R.G., Greupink, R.
• Format: Article
• Language: English
• Subjects: Ex vivo cotyledon perfusion; Pharmacokinetics; Placenta; Pregnancy; Renal transplantation; Tacrolimus
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2018.04.017

Currently, tacrolimus is the most potent immunosuppressive agent for renal transplant recipients and is commonly prescribed during pregnancy. As data on placental exposure and transfer are limited, we studied tacrolimus placental handling in samples obtained from renal transplant recipients. We found transfer to venous umbilical cord blood, but particularly noted a strong placental accumulation. In patient samples, tissue concentrations in a range of 55–82 ng/g were found. More detailed ex vivo dual-side perfusions of term placentas from healthy women revealed a tissue-to-maternal perfusate concentration ratio of 113 ± 49 (mean ± SEM), underlining the placental accumulation found in vivo. During the 3 h ex vivo perfusion interval no placental transfer to the fetal circulation was observed. In addition, we found a non-homogeneous distribution of tacrolimus across the perfused cotyledons. In conclusion, we observed extensive accumulation of tacrolimus in placental tissue. This warrants further studies into potential effects on placental function and immune cells of the placenta. [Display omitted]