Study of bioaccumulation of dalteparin at a prophylactic dose in patients with various degrees of impaired renal function.

摘要

BACKGROUND: Low-molecular-weight heparins (LMWH) have been shown to be effective and safe for prophylaxis of thromboembolic diseases. However, issues regarding safety and optimal use of LMWH arise in patients with renal insufficiency (RI). OBJECTIVES: To compare pharmacokinetic data of dalteparin for up to 3 weeks in patients with various degrees of RI. PATIENTS AND METHODS: Patients from general medical and surgical wards were included in this prospective cohort study and divided into three groups according to renal function: A=normal (GFR>or=60 mL min(-1)1.73 m(-2)), B=mild RI (GFR 30-59 mL min(-1)1.73 m(-2)), C=severe RI (GFR<30 mL min(-1)1.73 m(-2)). Dalteparin was injected s.c. once daily at a prophylactic dose. Peak anti-Xa activity levels (anti-Xa) were measured 4+/-1 h after injection on day 1 and every third day up to 3 weeks. Primary objectives were peak anti-Xa levels and adjusted anti-Xa levels, adjustment being carried out for dose and body weight. RESULTS: A total of 42 patients could be analyzed during a median of 10 days (interquartile range IQR 4-13, range 1-20). In all groups, adjusted peak anti-Xa levels were not different on day 10 compared with day 1. No bioaccumulation>30% could be found up to day 10 even in patients with severe RI. CONCLUSION: The use of dalteparin at a prophylactic dose was not associated with a bioaccumulation>30% even in patients with severe renal insufficiency during a median follow-up of 10 days (IQR 4-13, range 1-20).