The oral direct thrombin inhibitor, ximelagatran, an alternative for anticoagulant treatment during the puerperium and lactation.
OBJECTIVE
To determine the excretion of the oral direct thrombin inhibitor (oral DTI), ximelagatran, and its active form, melagatran, in human milk, and to thus evaluate the potential exposure of breastfed infants to melagatran.


METHODS
An open, single dose, single centre study.


METHODS
Department of Antenatal Care, Primary Health Care South Bohuslän and Institute for the Health of Women and Children, Göteborg University, Sweden.


METHODS
Seven healthy Caucasian breastfeeding women who were at least two months postpartum were studied.


METHODS
The concentrations of ximelagatran, its two intermediates, and melagatran were determined using liquid chromatography-mass spectrometry, with the limit of quantification of 2 nmol L(-1) for human milk and 10 nmol L(-1) for plasma concentrations.


METHODS
Concentrations of ximelagatran, its intermediates and melagatran were measured in breast milk over 72 hours, and in plasma over 12 hours, after a single oral 36 mg dose of ximelagatran.


RESULTS
Neither ximelagatran nor its intermediates were detected in human breast milk. Only trace amounts of melagatran were detected. The mean cumulative amount of melagatran excreted into breast milk over the 72-hour period after dosing with oral ximelagatran was 0.00091% of the administered dose of ximelagatran. Ximelagatran was well tolerated, with no clinically relevant changes in laboratory variables or vital signs.


CONCLUSIONS
Trace levels of melagatran are excreted in human breast milk following administration of the oral DTI ximelagatran. The exposure of breastfed infants to melagatran appears to be low and is therefore unlikely to be of clinical concern.
Hellgren
M
M
Department of Antenatal Care, Primary Health Care South Bohuslän and Institute for the Health of Women and Children, Sahlgrenska Hospital/East, University of Göteborg, S-416 85 Göteborg, Sweden.
Johansson
S
S
Eriksson
U G
UG
Wåhlander
K
K
D000284:Administration, Oral; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001384:Azetidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001596:Benzylamines; D001942:Breast Feeding; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007774:Lactation; D008895:Milk, Human / Q000737:chemistry*; D049590:Postpartum Period; D011644:Puerperal Disorders / Q000517:prevention & control; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013923:Thromboembolism / Q000517:prevention & control; D020246:Venous Thrombosis / Q000517:prevention & control
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C109573:melagatran; C426686:ximelagatran; D013917:Thrombin; D005998:Glycine