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Population pharmacokinetics analysis of patients receiving enoxaparin by continuous intravenous infusion
Author(s) -
Feng Y.,
Bies R. R.,
Bobek M. B.,
Kane S. L.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.112
Subject(s) - nonmem , pharmacokinetics , volume of distribution , medicine , covariate , population , body mass index , population pharmacokinetics , clinical pharmacology , body weight , distribution (mathematics) , pharmacology , statistics , mathematics , mathematical analysis , environmental health
Purpose To develop a population pharmacokinetic (PK) model for patients receiving continuous intravenous infusion (CI) of enoxaparin and compare results to the PK parameters reported for subcutaneous (SQ). Methods Anti‐Xa activity was measured in 48 patients receiving CI of enoxaparin. The population PK parameters were estimated by NONMEM. The effect of the covariates age, weight, height, creatinine clearance and sex were tested in the model. POSTHOC, model estimates were used to compare disposition in patients with three body mass index (BMI) categories: <24.9 kg m −2(n=18), 25 to 29.9 kg m −2 (n=19), >30 kg m −2(n=11). Results A one‐compartment linear model with additive and proportional error adequately described the data. Weight was a significant covariate on clearance (CL) for all estimation methods. The estimation of population CL and volume of distribution (Vd) were significantly higher than those reported for SQ (p<0.05), while the half‐life is longer than SQ. CL and half‐life increase as BMI increases, while the change in Vd was not statistically significant across groups (p>0.05). Conclusions PK parameters for CI are significantly different than those estimated SQ data. Body weight was a significant covariate for the model. Further studies should address issues of changing anti‐Xa activity dependent upon both route and rate of administration of enoxaparin. Clinical Pharmacology & Therapeutics (2004) 75 , P30–P30; doi: 10.1016/j.clpt.2003.11.112