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Tacrolimus placental transfer at delivery and neonatal exposure through breast milk.

MedStar author(s):

0306-5251

Name of journal: British journal of clinical pharmacologyAbstract: 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.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. 2013 The Authors. British Journal of Clinical Pharmacology 2013 The British Pharmacological Society.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.All authors: Calamia JC, Clark S, Davis CL, Easterling TR, Hays K, Hebert MF, Miodovnik M, Shen DD, Thummel KE, Umans JG, Zheng SFiscal year: FY2014Digital Object Identifier:

http://dx.doi.org/10.1111/bcp.12122

Date added to catalog: 2014-08-21

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Title notes ( 5 )

Holdings
Item type	Current library	Collection	Call number	Status	Date due	Barcode
Journal Article	MedStar Authors Catalog	Article	23528073	Available		23528073

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.

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. 2013 The Authors. British Journal of Clinical Pharmacology 2013 The British Pharmacological Society.

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.

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