The Pharmacokinetics of Subcutaneous Enoxaparin in End-Stage Renal Disease

The pharmacokinetics of enoxaparine, a low molecular weight heparin, was randomly studied in 12 healthy male volunteers. Doses of 20, 40, 60, and 80 mg were injected subcutaneously in randomized cross-over fashion. Anti-IIa and anti-Xa activities (using amidolytic methods), and calcium thrombin time, were measured over 36 hours. The maximum Amax of the anti-IIa and anti-Xa activities appeared 3 to 4 hours after administration. The terminal half-lives of anti-IIa and anti-Xa activities were approximately 2 and 4 hours, respectively, with no significant variation between the different doses. For the anti-Xa activity, there was a highly significant positive correlation between the dose injected and individual values of Amax (r = +0.915; P less than .001) and AUC (r = +0.913; P less than .001). Enoxaparine displays a relatively small apparent volume of distribution (about 7.0 L) and its total body clearance is about 1.25 L/hr. The mean residence time ranges from 4.6 to 7.6 hours. Thus, the pharmacokinetic profile of enoxaparine is characterized by a linear relationship between dose and absorption, a relatively low clearance and long elimination half-life, and a high anti-Xa/anti-IIa ratio.

To compare the frequency of bleeding complications from enoxaparin in patients with normal renal function versus patients with renal insufficiency. Retrospective chart review. University-based tertiary care center. One hundred six patients who received two or more doses of enoxaparin. Total bleeding complications occurred in 22% of patients with normal renal function and 51% with renal insufficiency (p<0.01). Major bleeds were also significantly different, 2% and 30%, respectively (p<0.001). No patients with normal renal function were given fresh-frozen plasma or packed red blood cells, whereas in those with renal insufficiency, 13% and 32%, respectively, received these products (p<0.01). Enoxaparin may have resulted in increased bleeding complications and use of blood products in patients with renal insufficiency. Prospective studies need to be conducted to define the drug's role and dosage adjustments in these patients.

This study investigates the pharmacokinetics of a low molecular weight heparin (Fraxiparine®) after a single bolus intravenous injection of 100 antifactor Xa IC U · kg -1 in 3 groups of patients affected by chronic renal insufficiency of various severity: group A (n = 7) was composed of hemodialyzed patients; group B (n = 7) had a creatinine clearance ranging from 10 to 20 ml · min -1 and group C (n = 5) from 30 to 50 ml · min -1 . There was no significant difference between the pharmacokinetic parameters determined in the 3 groups of patients and no correlation between these parameters and the creatinine clearance. However, when compared to the values established in a group of 12 healthy volunteers, the half-life of disappearance of the antifactor Xa activity was significantly prolonged. Therefore it is advised to monitor antifactor Xa activity in patients affected by chronic renal insufficiency of any severity to avoid a possible accumulation phenomenon.