Pharmacokinetics of enoxaparin in patients undergoing percutaneous coronary intervention with and without glycoprotein IIb/IIIa therapy.
The pharmacokinetic profile of enoxaparin was established in a substudy involving 1054 patients undergoing percutaneous coronary intervention. Patients enrolled in the National Investigators Collaborating on Enoxaparin 1 (NICE-1) trial received enoxaparin as a 1.0-mg/kg intravenous bolus. Patients enrolled in the NICE-4 trial received enoxaparin as a 0.75-mg/kg intravenous bolus followed by abciximab as a 0.25-mg/kg bolus and a 0.125-mcg/kg/min 12-hour infusion. Blood samples were collected at six time points over 12 hours and analyzed for plasma anti-Xa, anti-IIa, and Heptest (Haemachem Inc., St. Louis, MO) activity using specific and sensitive assay methods. Data were similar in both trials. Plasma anti-Xa, anti-IIa, and Heptest activity peaked shortly after the enoxaparin bolus and declined in parallel over the ensuing 12 hours. Area under the curve and peak activity were greatest for Heptest activity and least for anti-IIa activity. Values for clearance, volume of distribution, volume of distribution at steady state, and elimination rate constant were on the order of 10 mL/h/kg, 48 mL/kg, 45 mL/kg, and 0.22/h, respectively. These measures suggest that the use of abciximab in combination with enoxaparin during percutaneous coronary intervention is unlikely to affect the pharmacokinetics of enoxaparin.
Argenti
Domenick
D
Janssen Pharmaceutica, Titusville, New Jersey, USA. dargent1@prdus.jnj.com
Hoppensteadt
Debra
D
Heald
Donald
D
Jensen
Brad
B
Fareed
Jaweed
J
D000077284:Abciximab; D000328:Adult; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000925:Anticoagulants / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003327:Coronary Disease / Q000188:drug therapy* / Q000628:therapy; D004347:Drug Interactions; D017984:Enoxaparin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D007140:Immunoglobulin Fab Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077284:Abciximab