Milk transfer and neonatal safety of tacrolimus.
OBJECTIVE
To report the first case of tacrolimus measurement in human milk following maternal dosing in a woman who breast-fed while taking the medication.


METHODS
A 32-year-old white woman who had taken tacrolimus 0.1 mg/kg/d throughout pregnancy contacted the Motherisk Program at 35 weeks' gestation inquiring about the safety of breast-feeding during maternal tacrolimus therapy. After benefit-risk assessment, the mother decided to breast-feed the baby.


METHODS
Manually expressed milk samples were collected over 12 hours following the first tacrolimus dose of the day; pre-dosing and 1-hour post-dosing blood concentrations were also determined. The samples were analyzed for tacrolimus by tandem-mass spectrometry. Breast milk and blood samples were collected at steady-state.


RESULTS
The highest and mean concentrations of tacrolimus in milk were 0.57 and 0.429 ng/mL, respectively. From these measurements, the exclusively breast-fed infant would ingest, on average, 0.06 micro g/kg/d, which corresponds to 0.06% of the mother's weight-adjusted dose. Given the low oral bioavailability of tacrolimus, the maximum amount the baby would receive is 0.02% of the mother's weight-adjusted dose. The milk-to-blood ratios of tacrolimus at pre-dosing and 1-hour post-dosing concentrations were calculated to be 0.08 and 0.09, respectively. At 2.5 months of age, the infant was developing well both physically and neurologically.


CONCLUSIONS
This report is the first to measure tacrolimus concentrations in established human milk using tandem-mass spectrometry to detect drug while the infant was exclusively breast-fed by the mother, and in which the infant's growth and development were reported.


CONCLUSIONS
Our results suggest that maternal therapy with tacrolimus for liver transplant may be compatible with breast-feeding.
French
Amy E
AE
The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children and The University of Toronto, Toronto, Ontario, Canada.
Soldin
Steven J
SJ
Soldin
Offie P
OP
Koren
Gideon
G
D000328:Adult; D019540:Area Under Curve; D001942:Breast Feeding; D005260:Female; D006801:Humans; D007223:Infant; D008895:Milk, Human / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use
D016559:Tacrolimus