In vitro and in vivo evaluation of enoxaparin removal by continuous renal replacement therapies with acrylonitrile and polysulfone membranes.
BACKGROUND
Enoxaparin is a low-molecular-weight heparin for which the degree of elimination through hemofilters during continuous renal replacement therapy (CRRT) is not well established.


OBJECTIVE
The elimination of enoxaparin by CRRT, using acrylonitrile (AN69) or polysulfone (PS) membranes, was studied in vitro and among critically ill patients.


METHODS
In vitro procedures were carried out using Ringer's lactate, bovine albumin-containing Ringer's lactate, or fresh human plasma as enoxaparin vehicle, using AN69 or PS membranes, and following continuous veno-venous hemofiltration (CVVH) or continuous veno-venous hemodialysis (CVVHD). Prefilter and ultrafiltrate samples were collected over 60 minutes. All procedures were carried out in triplicate. Patients undergoing CRRT entered the in vivo study. Enoxaparin was administered subcutaneously once daily. The sieving coefficient (Sc) and saturation coefficient (Sa) were calculated as the relation between anti-factor Xa activity in simultaneously collected dialysate/ultrafiltrate samples and plasma samples.


RESULTS
Mean Sc (for CVVH) or Sa (for CVVHD) values in the in vitro procedures ranged from 0.16 to 0.57. Sc values during CVVH were significantly higher than Sa values during CVVHD in the Ringer's lactate procedures for both membranes (AN69 membrane, P = 0.014; PS membrane, P < 0.001) and in the plasma procedures with the PS membrane (P < 0.001). Six male and 2 female patients (all white) participated in the in vivo study. Their mean body weight ranged from 55 to 80 kg, and their age ranged from 71 to 82 years. In patients, Sc or Sa achieved values between 0.26 and 0.67. No significant differences were found in vivo in the permeability of the 2 membranes to enoxaparin.


CONCLUSIONS
In these studies, the Sc and Sa values suggested that enoxaparin passed through AN69 and PS membranes during CRRT. Further pharmacokinetic and clinical studies are needed to determine whether a dose adjustment for enoxaparin is needed for patients undergoing CRRT.
Isla
Arantxazu
A
Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Vitoria-Gasteiz, Spain.
Gascón
Alicia R
AR
Maynar
Javier
J
Arzuaga
Alazne
A
Corral
Esther
E
Martín
Alejandro
A
Solinís
María Angeles
MA
Muñoz
José Luis Pedraz
JL
D000181:Acrylonitrile / Q000737:chemistry*; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D017984:Enoxaparin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D065427:Factor Xa Inhibitors; D005260:Female; D006440:Hemofiltration / Q000295:instrumentation*; D006801:Humans; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000737:chemistry; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D008297:Male; D008567:Membranes, Artificial; D010539:Permeability; D011108:Polymers / Q000737:chemistry*; D011485:Protein Binding; D006435:Renal Dialysis / Q000295:instrumentation*; D000077325:Ringer's Lactate; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013450:Sulfones / Q000737:chemistry*
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D007552:Isotonic Solutions; D008567:Membranes, Artificial; D011108:Polymers; D000077325:Ringer's Lactate; D013450:Sulfones; C017662:polysulfone P 1700; D012710:Serum Albumin, Bovine; D000181:Acrylonitrile