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Anti‐factor Xa kinetics after intravenous enoxaparin in patients undergoing percutaneous coronary intervention: a population model analysis
Author(s) -
SanchezPena Paola,
Hulot JeanSébastien,
Urien Saïk,
Ankri Annick,
Collet JeanPhilippe,
Choussat Rémi,
Lechat Philippe,
Montalescot Gilles
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02452.x
Subject(s) - medicine , bolus (digestion) , percutaneous coronary intervention , pharmacokinetics , conventional pci , dosing , population , anesthesia , pharmacodynamics , myocardial infarction , environmental health
Aim Recent studies have suggested that intravenous (i.v.) enoxaparin could be used as antithrombotic therapy in patients ongoing percutaneous coronary intervention (PCI). However, anti‐Xa pharmacokinetics following different i.v. dosing regimens is not clearly established. Methods A population pharmacokinetic analysis was developed using anti‐Xa activities measured in 546 patients who received a single 0.5 mg kg −1 i.v. dose of enoxaparin immediately before PCI. Effects of higher doses (0.75 mg kg −1 and 1 mg kg −1 ) and/or additional bolus after the initial administration were similarly simulated. Results Enoxaparin anti‐Xa time profiles were best described by a one‐compartment model with zero‐order kinetics. Mean population parameters (intersubject variability, %) were CL 1.2 l h −1 (33), V 2.9 l (30) and zero‐order input 0.25 h (24). With a single bolus of 0.5 mg kg −1 , the totality of the patients reached an effective anticoagulation level (anti‐Xa >0.5 IU ml −1 ) and only 2.5% reached levels above 1.5 IU ml −1 . Simulations showed that greater doses (0.75 mg kg −1 and 1 mg kg −1 ) prolonged the duration of anticoagulation (3.4 and 4.1 h, respectively) compared with the 0.5 mg kg −1 bolus (2.7 h) and markedly increased the proportion (48% and 79%, respectively) of patients with anti‐Xa levels >1.5 IU ml −1 . For delayed and/or prolonged procedures, patients could be administered a second bolus of half the initial dose in a time interval between 90 min to 2 h after in order to maintain similar anticoagulation profile levels. Conclusions A single 0.5 mg kg −1 i.v. dose of enoxaparin reached anticoagulation levels adequately and should be safer compared with greater doses for anticoagulation in patients undergoing an elective PCI. An additional second bolus could be proposed in patients with delayed or prolonged procedures.