Tacrolimus placental transfer at delivery and neonatal exposure through breast milk.
Citation: British Journal of Clinical Pharmacology. 76(6):988-96, 2013 Dec.PMID: 23528073Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *Delivery, Obstetric | *Immunosuppressive Agents/pk [Pharmacokinetics] | *Milk, Human/ch [Chemistry] | *Organ Transplantation | *Placenta/me [Metabolism] | *Tacrolimus/pk [Pharmacokinetics] | Adult | Breast Feeding | Female | Fetal Blood/ch [Chemistry] | Humans | Immunosuppressive Agents/ad [Administration & Dosage] | Immunosuppressive Agents/bl [Blood] | Immunosuppressive Agents/tu [Therapeutic Use] | Infant, Newborn | Placental Circulation | Pregnancy | Tacrolimus/ad [Administration & Dosage] | Tacrolimus/bl [Blood] | Tacrolimus/tu [Therapeutic Use]Year: 2013ISSN:- 0306-5251
Item type | Current library | Collection | Call number | Status | Date due | Barcode |
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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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