Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy.
OBJECTIVE
We sought to evaluate the pharmacokinetics of subcutaneously administered enoxaparin sodium during and after pregnancy.


METHODS
Daily subcutaneous injections of enoxaparin sodium (40 mg) were administered to 13 pregnant women. On 3 separate occasions, once early in pregnancy (12-15 weeks), once late in pregnancy (30-33 weeks), and once in the nonpregnant state (6-8 weeks post partum), serial blood samples were collected, and plasma was analyzed for antifactor Xa activity. Analysis of variance was used for statistical analysis. P <.05 was significant.


RESULTS
The time to maximum concentration and the mean residence time in pregnancy compared with the postpartum state were not significantly different. During early and late pregnancy, maximum concentration and the last measurable anti-factor Xa activity level were lower than in the nonpregnant state (P <.05). The area under the plasma activity-versus-time curve was significantly lower in pregnancy than in the postpartum state (P <.05).


CONCLUSIONS
The pharmacokinetics of enoxaparin sodium are significantly different during pregnancy than in the same women when nonpregnant. The observed difference is likely because of increased renal clearance of enoxaparin during pregnancy. This finding has significant implications for appropriate dosing of enoxaparin in pregnancy.
Casele
H L
HL
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Medical School, Evanston, Illinois, USA.
Laifer
S A
SA
Woelkers
D A
DA
Venkataramanan
R
R
D000328:Adult; D000704:Analysis of Variance; D017984:Enoxaparin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D019476:Insect Proteins; D008970:Molecular Weight; D049590:Postpartum Period / Q000097:blood; D011247:Pregnancy; D018566:Pregnancy, High-Risk / Q000097:blood*; D012471:Salivary Proteins and Peptides / Q000097:blood; D013997:Time Factors
D017984:Enoxaparin; D005343:Fibrinolytic Agents; D019476:Insect Proteins; D012471:Salivary Proteins and Peptides; C114100:anticoagulant factor Xa protein, Aedes aegypti