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. DESIGN: An open, single dose, single centre study. SETTING: Department of Antenatal Care, Primary Health Care South Bohuslan and Institute for the Health of Women and Children, Goteborg University, Sweden. SAMPLE: 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. MAIN OUTCOME MEASURES: 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.

Nyckelord

Administration

Oral

Adult

Anticoagulants/administration & dosage/*pharmacokinetics

Azetidines/administration & dosage/*pharmacokinetics

Benzylamines

*Breast Feeding

Female

Glycine/*analogs & derivatives/*analysis/metabolism

Humans

Lactation

Milk

Human/*chemistry

Postpartum Period

Puerperal Disorders/prevention & control

Thrombin/*antagonists & inhibitors

Thromboembolism/prevention & control

Venous Thrombosis/prevention & control

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)