Farmacocinética y farmacodinámica de la bivalirudina: efecto de la función renal, la dosis y el sexo

BACKGROUND: These studies were conducted to determine whether bivalirudin clearance and pharmacodynamics are dependent on dose, renal function, or gender. METHODS: Two studies were performed. The first comprised 25 patients who were undergoing percutaneous coronary intervention-8 with normal renal function, 11 with mild renal impairment, and 6 with moderate renal impairment. Each patient received a bolus dose of bivalirudin (1 mg/kg) followed by an infusion (2.5 mg/kg per hour for 4 of 6 hours, then 0.5 mg/kg per hour for 4 of 6 hours). The second study enrolled 8 volunteers with severe renal impairment who received a bivalirudin bolus of 1 mg/kg, followed by an infusion of 0.5 mg/kg per hour for 10 hours. Bivalirudin in plasma and urine was assayed with a newly developed, highly specific liquid chromatography-mass spectrometry assay. RESULTS: Clearances at the two infusion doses did not differ significantly (3.23 mL/min per kilogram and 3.16 mL/min per kilogram). There was no statistically significant difference in area under the concentration-time curve (AUC) and in plasma clearance between patients with normal renal function and those with mild renal impairment. Patients with moderate and severe renal impairment had reductions in plasma clearance of 21% and 24%, respectively. The level of anticoagulation(activated clotting time) was similar between groups. There was no difference between male and female patients. CONCLUSION: The clearance of bivalirudin is dependent on renal function but independent of dose and gender. Approximately 20% of unchanged drug is cleared via the kidney, and the remainder presumably undergoes proteolysis intracellularly. The pharmacodynamics of bivalirudin are dose-dependent and gender-independent. Bivalirudin kinetics are linear in the dose ranges that are used in percutaneous coronary intervention and that are under investigation for use in acute coronary syndromes.

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Dos estudios evaluaron la bivalirudina. El primero incluyó 25 pacientes de ICP (8 con función renal normal, 11 con insuficiencia leve y 6 moderada) con bolo 1 mg/kg e infusión de 2,5 y luego 0,5 mg/kg/h; el segundo, 8 voluntarios con insuficiencia grave (bolo 1 mg/kg, 0,5 mg/kg/h por 10 h). El aclaramiento no dependió de la dosis (3,23 vs. 3,16 ml/min/kg) ni del sexo, pero cayó un 21 % y 24 % en insuficiencia moderada y grave.

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