The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers.
OBJECTIVE
The objective of this study was to compare the pharmacokinetics of the low-molecular-weight heparin enoxaparin in obese and nonobese volunteers, by means of two administration regimens.


METHODS
Enoxaparin was administered subcutaneously (1.5 mg/kg once daily for 4 days) and in a single 6-hour infusion (1.5 mg/kg) to 24 obese volunteers and 24 age-, sex-, and height-matched nonobese volunteers in a randomized, open-label, 2-way crossover design. Blood plasma was assessed for anti-Xa and anti-IIa activity and activated partial thromboplastin time.


RESULTS
After subcutaneous administration, steady-state exposure was achieved after the second dose in nonobese volunteers and after the third dose in obese volunteers. Time to maximum anti-Xa activity was 1 hour longer in obese volunteers, but maximum anti-Xa activity was similar in both groups. For anti-Xa activity, exposure at steady-state was 16% higher in obese volunteers than in nonobese volunteers (90% confidence interval, 108%-125%). After intravenous infusion, total body clearance and volume of distribution at steady state were higher in obese volunteers than in nonobese volunteers, but when adjusted for weight, these values were about 10% lower in obese volunteers. Anti-IIa activity after subcutaneous administration did not differ significantly between obese and nonobese volunteers. Pharmacodynamic analysis of activated partial thromboplastin time showed similar results in obese and nonobese volunteers after both intravenous and subcutaneous administration. No deaths or serious adverse events occurred during the study.


CONCLUSIONS
Enoxaparin was well tolerated when administered subcutaneously or intravenously, and there appears to be no need to modify the currently recommended dose for obese volunteers.
Sanderink
Ger-Jan
GJ
Department of Drug Metabolism and Pharmacokinetics, Aventis Pharma, Vitry-Alfortville, France. ger.sanderink@aventis.com
Le Liboux
Aimé
A
Jariwala
Navin
N
Harding
Neasa
N
Ozoux
Marie-Laure
ML
Shukla
Umesh
U
Montay
Guy
G
Boutouyrie
Bruno
B
Miro
Adelaida
A
D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000097:blood; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D065427:Factor Xa Inhibitors; D006805:Human Experimentation; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000037:antagonists & inhibitors; D012737:Sex Factors; D018709:Statistics, Nonparametric
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D011516:Prothrombin