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Study of bioaccumulation of dalteparin at a therapeutic dose in patients with renal insufficiency
Author(s) -
SCHMID P.,
BRODMANN D.,
ODERMATT Y.,
FISCHER A. G.,
WUILLEMIN W. A.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03556.x
Subject(s) - medicine , interquartile range , renal function , low molecular weight heparin , therapeutic index , pharmacokinetics , prospective cohort study , urology , gastroenterology , pharmacology , heparin , drug
Summary. Background : Low‐molecular‐weight heparins (LMWH) are effective, safe and convenient for anticoagulation. Their use is limited in patients with renal insufficiency (RI) because of bioaccumulation. Objectives : Evaluate pharmacokinetic data of dalteparin at a therapeutic dose in patients with RI. Patients and methods : Prospective observational cohort study. Inpatients were included into three groups according to glomerular filtration rate (GFR): A ≥ 60, B 30–59, C < 30 mL min −1 1.73 m −2 . Dalteparin was injected subcutaneously (s.c.) twice daily. Peak plasma anti‐factor Xa activity (anti‐Xa) was measured and adjusted to applied dose and body weight after the first dose, on day 2, and every 2nd day afterwards. Bioaccumulation factor R was calculated as quotient of the last and the first adjusted anti‐Xa. Data are shown as median (interquartile range, IQR). Results : Thirty‐two patients (23 men) receiving dalteparin for ≥ 2 days were analyzed. Follow‐up was 6 days (IQR 4–10, range 2–22). Median dose was 90 (73–106) units kg −1 per 12 h ( P = 0.68). After the first dose, adjusted anti‐Xa levels were 3.5 (2.6–5.0), 4.8 (3.3–5.5), 4.5 (3.7–7.5) × 10 −3 for the groups A, B, C; P = 0.26. On the last day, they were 6.1 (3.7–7.3), 7.1 (5.6–8.3), 10.2 (7.8–13.2) × 10 −3 ; A compared with C, P = 0.002. R was 1.46 (1.15–1.82), 1.36 (1.20–2.16) and 2.28 (1.53–2.93); A compared with C, P = 0.18. Conclusion : Therapeutically dosed dalteparin accumulates in patients with severe RI (group C). Dose adjustments according to anti‐Xa are recommended for dalteparin if used in this patient population. However, no simple dosing scheme can be suggested yet because of wide inter‐individual variation.