title: The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers.
abstract: 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.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Aventis Pharma, Vitry-Alfortville, France. ger.sanderink@aventis.com
authors.forename: Ger-Jan
authors.initials: GJ
authors.lastname: Sanderink
authors.forename: Aimé
authors.initials: A
authors.lastname: Le Liboux
authors.forename: Navin
authors.initials: N
authors.lastname: Jariwala
authors.forename: Neasa
authors.initials: N
authors.lastname: Harding
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Ozoux
authors.forename: Umesh
authors.initials: U
authors.lastname: Shukla
authors.forename: Guy
authors.initials: G
authors.lastname: Montay
authors.forename: Bruno
authors.initials: B
authors.lastname: Boutouyrie
authors.forename: Adelaida
authors.initials: A
authors.lastname: Miro
mesh_terms: 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
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D011516:Prothrombin