Reliable anticoagulation with enoxaparin in patients undergoing percutaneous coronary intervention: The pharmacokinetics of enoxaparin in PCI (PEPCI) study.

The objective of this study was to evaluate the pharmacokinetic response to intravenous (IV) enoxaparin given 8-12 hr after subcutaneous (SC) dosing in patients undergoing percutaneous coronary intervention (PCI). Fifty-five patients received SC enoxaparin (1 mg/kg every 12 hr) followed by an IV bolus (0.3 mg/kg) 8-12 hr after the last SC dose, at the start of PCI or during catheterization. Anti-Xa levels were within the target range in 98% of patients 2-8 hr after the last SC dose, in 96% of patients following the IV bolus, and in 91% of patients for a further 2 hr. Subcutaneous enoxaparin (1 mg/kg every 12 hr) provides sufficient anti-Xa levels for PCI 2-8 hr after the last dose. An additional 0.3 mg/kg enoxaparin dose given IV 8-12 hr after the last SC dose reliably maintains anti-Xa levels within the target for at least 2 additional hr.

Pharmacokinetics and pharmacodynamics of the prophylactic dose of enoxaparin once daily over 4 days in patients with renal impairment.

The pharmacokinetics of the low-molecular-weight heparin enoxaparin were evaluated in 12 healthy volunteers and 36 patients with mild, moderate or severe renal impairment. Enoxaparin was administered once daily by subcutaneous injections at a dose of 40 mg for 4 days and venous blood samples were taken over a 5-day period to determine antifactor Xa and antifactor IIa activity and the activated partial thromboplastin time. Adverse events were also recorded. The results for anti-Xa activity showed that the rate of absorption of enoxaparin was similar across the four groups of study participants. The elimination half-life increased with the degree of renal impairment, and this relationship was more evident after repeated dosing. Anti-Xa exposure was not significantly different between healthy volunteers and patients with mild or moderate renal impairment, but was significantly increased in patients with severe renal impairment (creatinine clearance < or =30 ml/min). Anti-Xa clearance decreased with the degree of renal impairment after repeated dosing, but only the difference between patients with severe renal impairment and healthy volunteers was statistically significant, the clearance on Day 4 being 39% lower in patients with severe renal impairment than in healthy volunteers (P=.0001). Anti-IIa activity was low in all study participants, and the activated partial thromboplastin time was not significantly different between the study groups. In conclusion, the clearance of enoxaparin is reduced in patients with severe renal impairment. Dose adjustment of enoxaparin may need to be recommended in these patients, but no recommendation can be made in patients with mild or moderate renal impairment.