Influence of patient characteristics and renal function on factor Xa inhibition pharmacokinetics and pharmacodynamics after enoxaparin administration in non-ST-segment elevation acute coronary syndromes.
BACKGROUND
The current standard of care for patients with non-ST-segment elevation acute coronary syndromes (ACS) includes antithrombotic therapy with aspirin and heparin. Although emerging data suggest that low-molecular weight preparations offer distinct advantages over unfractionated heparin, limited information on patient-related factors that may influence dosing, safety, and efficacy is available.


OBJECTIVE
The purpose of our study was the determination of the impact of patient age, sex, body weight, and renal function on factor Xa inhibition pharmacokinetics and pharmacodynamics after enoxaparin administration in patients with ACS.


RESULTS
Patients enrolled in the TIMI 11A trial received a full complement of antiischemic therapy, aspirin, and enoxaparin (30 mg intravenously, followed by weight-adjusted doses of either 1 mg/kg or 1.25 mg/kg subcutaneously every 12 hours). Before and after the third and last doses, blood samples were obtained from 445 patients for measurement of anti-Xa activity. The mean apparent clearance, distribution volume, and plasma half-life were 0.733 L/h, 5.24 L, and 5 hours, respectively. Among a wide range of clinical and laboratory covariates, creatinine clearance emerged as the most influential factor on apparent clearance, area under the curve, and anti-Xa activity. Patients with marked renal impairment (creatinine clearance <40 mL/min) had higher trough and peak anti-Xa activity compared with those with normal renal function and were more likely to have major hemorrhagic events.


CONCLUSIONS
The pharmacokinetic and pharmacodynamic profiles after enoxaparin administration are consistent across a broad range of patients with ACS. Dose adjustments or anti-Xa coagulation monitoring or both will be necessary rarely in routine clinical practice, with the exception of patients with severe renal insufficiency.
Becker
Richard C
RC
Cardiovascular Thrombosis Research Center, Division of Cardiology, University of Massachusetts Medical School, Boston 01655, USA.
Spencer
Frederick A
FA
Gibson
Michael
M
Rush
Janet E
JE
Sanderink
Gerard
G
Murphy
Sabina A
SA
Ball
Steven P
SP
Antman
Elliott M
EM
D000367:Age Factors; D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D019540:Area Under Curve; D001241:Aspirin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015415:Biomarkers; D001835:Body Weight; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications*; D003404:Creatinine / Q000378:metabolism; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007668:Kidney / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D012737:Sex Factors; D013577:Syndrome
D015415:Biomarkers; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D003404:Creatinine; D001241:Aspirin