Tacrolimus placental transfer at delivery and neonatal exposure through breast milk

Songmao Zheng, Thomas R. Easterling, Karen Hays, Jason G. Umans, Menachem Miodovnik, Shannon Clark, Justina C. Calamia, Kenneth E. Thummel, Danny D. Shen, Connie L. Davis, Mary F. Hebert

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Aim(s) The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. Methods Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. Results Mean (±SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 ± 1.8 ng ml-1) were 71 ± 18% (range 45-99%) of maternal concentrations (9.0 ± 3.4 ng ml-1). The mean umbilical cord venous plasma (0.09 ± 0.04 ng ml-1) and unbound drug concentrations (0.003 ± 0.001 ng ml-1) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 ± 12% of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3% of the mother's weight-adjusted dose. Conclusions Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant.

Original languageEnglish (US)
Pages (from-to)988-996
Number of pages9
JournalBritish Journal of Clinical Pharmacology
Volume76
Issue number6
DOIs
StatePublished - Dec 2013

Fingerprint

Tacrolimus
Human Milk
Mothers
Fetal Blood
Umbilical Cord
Umbilicus
Breast Feeding
Hematocrit
Pharmaceutical Preparations
Allografts
Pharmacokinetics
Erythrocytes
Weights and Measures
Health

Keywords

  • breast milk
  • neonatal exposure
  • placental transfer
  • pregnancy
  • tacrolimus
  • unbound drug concentration

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Zheng, S., Easterling, T. R., Hays, K., Umans, J. G., Miodovnik, M., Clark, S., ... Hebert, M. F. (2013). Tacrolimus placental transfer at delivery and neonatal exposure through breast milk. British Journal of Clinical Pharmacology, 76(6), 988-996. https://doi.org/10.1111/bcp.12122

Tacrolimus placental transfer at delivery and neonatal exposure through breast milk. / Zheng, Songmao; Easterling, Thomas R.; Hays, Karen; Umans, Jason G.; Miodovnik, Menachem; Clark, Shannon; Calamia, Justina C.; Thummel, Kenneth E.; Shen, Danny D.; Davis, Connie L.; Hebert, Mary F.

In: British Journal of Clinical Pharmacology, Vol. 76, No. 6, 12.2013, p. 988-996.

Research output: Contribution to journalArticle

Zheng, S, Easterling, TR, Hays, K, Umans, JG, Miodovnik, M, Clark, S, Calamia, JC, Thummel, KE, Shen, DD, Davis, CL & Hebert, MF 2013, 'Tacrolimus placental transfer at delivery and neonatal exposure through breast milk', British Journal of Clinical Pharmacology, vol. 76, no. 6, pp. 988-996. https://doi.org/10.1111/bcp.12122
Zheng, Songmao ; Easterling, Thomas R. ; Hays, Karen ; Umans, Jason G. ; Miodovnik, Menachem ; Clark, Shannon ; Calamia, Justina C. ; Thummel, Kenneth E. ; Shen, Danny D. ; Davis, Connie L. ; Hebert, Mary F. / Tacrolimus placental transfer at delivery and neonatal exposure through breast milk. In: British Journal of Clinical Pharmacology. 2013 ; Vol. 76, No. 6. pp. 988-996.
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abstract = "Aim(s) The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. Methods Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. Results Mean (±SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 ± 1.8 ng ml-1) were 71 ± 18{\%} (range 45-99{\%}) of maternal concentrations (9.0 ± 3.4 ng ml-1). The mean umbilical cord venous plasma (0.09 ± 0.04 ng ml-1) and unbound drug concentrations (0.003 ± 0.001 ng ml-1) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 ± 12{\%} of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3{\%} of the mother's weight-adjusted dose. Conclusions Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant.",
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AU - Clark, Shannon

AU - Calamia, Justina C.

AU - Thummel, Kenneth E.

AU - Shen, Danny D.

AU - Davis, Connie L.

AU - Hebert, Mary F.

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N2 - Aim(s) The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. Methods Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. Results Mean (±SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 ± 1.8 ng ml-1) were 71 ± 18% (range 45-99%) of maternal concentrations (9.0 ± 3.4 ng ml-1). The mean umbilical cord venous plasma (0.09 ± 0.04 ng ml-1) and unbound drug concentrations (0.003 ± 0.001 ng ml-1) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 ± 12% of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3% of the mother's weight-adjusted dose. Conclusions Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant.

AB - Aim(s) The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. Methods Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. Results Mean (±SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 ± 1.8 ng ml-1) were 71 ± 18% (range 45-99%) of maternal concentrations (9.0 ± 3.4 ng ml-1). The mean umbilical cord venous plasma (0.09 ± 0.04 ng ml-1) and unbound drug concentrations (0.003 ± 0.001 ng ml-1) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 ± 12% of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3% of the mother's weight-adjusted dose. Conclusions Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant.

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