Anti‐factor Xa kinetics after intravenous enoxaparin in patients undergoing percutaneous coronary intervention: a population model analysis

Abstract

AimRecent 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. MethodsA 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. ResultsEnoxaparin 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. ConclusionsA 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. Intravenous enoxaparin in patients undergoing PCIBr J Clin Pharmacol 60 :4 365

Safety and efficacy of intravenous enoxaparin for carotid endarterectomy: A prospective randomized pilot trial

“…26 Thus, body weight-adjusted dosing does appear to be more useful. All these effects imply that enoxaparin may be a more reliable and predictable alternative to UFH; however, comparing anticoagulation effects for these heparins is difficult.…”

“…25 When given intravenously, enoxaparin at 0.5 mg/kg reaches a desired anticoagulation for only up to 2 hours. 26 In the current study, the mean body weight-adjusted dose of UFH was 69.4 Ϯ 12.7 IU/kg for all patients. The body weight-adjusted doses of heparin for the three patients with bleeding complications were 62.5, 71, and 74 IU/kg and thus well within the suggested range for optimal anticoagulation.…”

Enoxaparin Anticoagulation Monitoring in the Catheterization Laboratory Using a New Bedside Test

“…Several studies have shown that an SQ upstream treatment by enoxaparin at the dose of 1 mg/kg twice daily (0.65 mg/kg twice daily for patients with impaired renal function) allows adequate anticoagulation for PCI within 8 h of the last injection, whereas an additional IV bolus of 0.25 to 0.30 mg/kg is needed (13,15,16) if the last SQ was injected more than 8 h and less than 12 h before the procedure. Our work confirms that this enoxaparin dose regimen is associated with an anti-Xa activity in the therapeutic range (0.5 to 1.8 IU/ml) in the large majority of patients (95%) with low rates of under-or over-anticoagulated patients (4% and 1%, respectively).…”

Reduced Thrombin Generation and Soluble P-selectin After Intravenous Enoxaparin During PCI

“…A simulated study based on the kinetics of F Xa inhibition after 0.5 mg/kg i.v. dose of enoxaparin [17] reported that after the i.v. dose of 0.75 mg/kg applied before PCI, the anticoagulation effects of enoxaparin >0.5 IU/ml persisted for 3.4±1.1 h and 28% of patients achieved initial inhibition higher than 1.8 IU/ml [13,14].…”