Pharmacodynamics assessment of Bemiparin after multiple prophylactic and single therapeutic doses in adult and elderly healthy volunteers and in subjects with varying degrees of renal impairment

Introduction: Aging and renal impairment may prolong the half-life and lead to accumulation of low molecular weight heparins. Correct dosing is critical to prevent bleeding or thrombosis. Materials and Methods: Open, parallel study. Healthy adult [n = 13] and elderly (>65 yrs) [n = 12] volunteers; and subjects with mild (Cl-Cr >= 50 to <= 80 mL/min ,n = 8), moderate (Cl-Cr >= 30 to b50 mL/min, n = 7), and severe (Cl-Cr < 30 mL/min, n = 8) renal impairment received four prophylactic doses (3,500 IU/24 h) and a single therapeutic dose (115 IU/kg) of bemiparin with an interim washout period. Anti-FXa activity and the potential need for dose adjustment were evaluated. Results: There were statistically significant differences in the severe renal impairment group vs. adult volunteers in all anti-FXa related parameters, but no significant differences in any of the anti-FXa related parameters between the adult and the elderly. Anti-FXa simulations after 10 prophylactic doses predicted mean A(max) = 0.59 IU/mL in subjects with severe renal impairment and 0.33-0.39 IU/mL in the rest. Simulations in the severe renal impairment group with dose adjustment (2,500 IU/24 h) predicted all individual A(max) < 0.60 IU/mL (mean A(max) = 0.42 IU/ml). Simulations after 10 therapeutic doses predicted mean A(max) = 1.22 IU/mL in severe renal impairment group and 0.89-0.98 IU/mL in the rest. Simulations in the severe renal impairment group with 75% dose adjustment predicted individual A(max) <= 1.60 IU/mL (mean A(max) = 0.91 IU/mL). Conclusions: No dose adjustments are required in elderly with preserved renal function. A dose adjustment of bemiparin is only advisable in patients with severe renal impairment when using prophylactic or therapeutic doses. (C) 2014 Elsevier Ltd. All rights reserved.