title: Evaluation and Pharmacokinetics of Treatment Dose Enoxaparin in Hospitalized Patients With Morbid Obesity.
abstract: BACKGROUND
  The pharmacokinetic properties of enoxaparin may lead to supratherapeutic antifactor Xa (anti-Xa) levels and increased bleeding when standard treatment doses are used in patients with morbid obesity.
  
  
  OBJECTIVE
  To evaluate the dose of enoxaparin needed to achieve therapeutic anti-Xa levels in a prospective, masked observational cohort of heterogeneous inpatients with morbid obesity and to determine whether patients with morbid obesity treated with 1 mg/kg of enoxaparin are at increased risk of supratherapeutic levels and bleeding events compared to patients receiving lower doses.
  
  
  METHODS
  Hospitalized patients with a body mass index ≥40 kg/m(2) or actual body weight ≥140 kg and prescribed treatment doses of enoxaparin >60 mg per day were enrolled and consented to phlebotomy for determination of anti-Xa levels.
  
  
  RESULTS
  Forty-one patients were included for data analysis. The dose of enoxaparin that resulted in therapeutic and supratherapeutic anti-Xa levels at steady state was 0.83 mg/kg and 0.98 mg/kg (-0.11; 95% confidence interval [CI] -0.20 to -0.01, P = .02), respectively. Enoxaparin dose as mg/kg of actual body weight was an independent predictor of having a supratherapeutic anti-Xa level. Patients with doses <0.95 mg/kg versus ≥0.95 mg/kg were less likely to have supratherapeutic levels (odds ratio 0.21 [95% CI 0.05-0.84], P = .02) and had similar rates of subtherapeutic levels. Doses <0.95 mg/kg and ≥0.95 mg/kg resulted in similar bleeding rates of 17.9% and 22.2% (P = .71), respectively.
  
  
  CONCLUSIONS
  Patients with morbid obesity required less than the recommended 1 mg/kg enoxaparin dose to achieve therapeutic peak anti-Xa levels; therefore, initiation with lower dosages is prudent and anti-Xa monitoring should guide dosage adjustments.
authors.affiliation: Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA nthompson-moore@houstonmethodist.org.
authors.forename: Nathaniel R
authors.initials: NR
authors.lastname: Thompson-Moore
authors.affiliation: Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Wanat
authors.affiliation: Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Putney
authors.affiliation: Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Phuong H Nguyen
authors.initials: PH
authors.lastname: Liebl
authors.affiliation: Department of Pathology, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Chandler
authors.affiliation: Department of Medicine, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Muntz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood* / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D017984:Enoxaparin; D065427:Factor Xa Inhibitors
keywords: anticoagulation; obesity; pharmacodynamics; pharmacokinetics; population pharmacokinetics