Pharmacokinetics of low molecular weight heparin and unfractionated heparin in pregnancy.
OBJECTIVE
Little pharmacokinetic data are available for either low molecular weight heparins (LMWHs) or unfractionated heparins (UFHs) in pregnancy. The objectives of this study were to determine whether differences exist in the pharmacokinetics of dalteparin and UFH before and during the first, second, and third trimesters of pregnancy in women with the antiphospholipid antibody syndrome (APS). Adjustments in our dosing protocol would be made if differences existed.


METHODS
Women with APS who were contemplating pregnancy were randomized to dalteparin 2500 U, 2500 U, 5000 U, and 7500 U daily, or UFH 5000 U, 5000 U, 7500 U, and 10,000 U every 12 hours, prior to pregnancy and the first, second, and third trimesters, respectively. Serial plasma concentrations of heparin were measured during 4 blood sampling days by determining anti-factor Xa activity.


RESULTS
Fifteen (n = 9 receiving dalteparin and n = 6 receiving UFH) completed all four sampling periods. For dalteparin, significant differences (P <.05) were detected, using area under the curve (AUC), between pre-pregnancy versus third trimester, first versus second trimester, first versus third trimester, and second versus third trimester. No significant differences were detected in the UFH group.


CONCLUSIONS
In APS, our original dosing protocol of dalteparin yielded significant differences (P <.05) in drug exposure throughout pregnancy. Based on these results, we recommend a prophylactic dalteparin dosing regimen of 2500 U every 24 hours pre-pregnancy (and for 6 weeks postpartum), and 5000 U every 24 hours during the first, second, and third trimesters. Due to lack of significant differences in AUC throughout pregnancy for UFH, we recommend continuing with our original dosing protocol.
Ensom
Mary H H
MH
Faculty of Pharmaceutical Sciences and Department of Obstetrics and Gynaecology, University of British Columbia, Canada. ensom@interchange.ubc.ca
Stephenson
Mary D
MD
D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016736:Antiphospholipid Syndrome / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011264:Pregnancy Trimesters
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin