Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

12.2 Pharmacodynamics
In healthy volunteers and patients (with ≥70% vessel occlusion undergoing routine PTCA), bivalirudin exhibited dose- and concentration-dependent anticoagulant activity as evidenced by prolongation of the ACT, aPTT, PT, and TT.
Intravenous administration of bivalirudin produces an immediate anticoagulant effect. Coagulation times return to baseline approximately 1 hour following cessation of bivalirudin administration. Bivalirudin Medi-Market 250 mg also increases INR. Therefore INR measurements made in bivalirudin Medi-Market 250 mg treated patients may not be useful for determining the appropriate dose of warfarin.

In 291 patients with ≥70% vessel occlusion undergoing routine PTCA, a positive correlation was observed between the dose of bivalirudin and the proportion of patients achieving ACT values of 300 sec or 350 sec. At a bivalirudin dose of 1 mg/kg IV bolus plus 2.5 mg/kg/h IV infusion for 4 hours, followed by 0.2 mg/kg/h, all patients reached maximal ACT values >300 sec.

Pharmacokinetic Properties

12.3 Pharmacokinetics
Bivalirudin exhibits linear pharmacokinetics following IV administration to patients undergoing PTCA. In these patients, a mean steady state bivalirudin concentration of 12.3 ± 1.7 mcg/mL is achieved following an IV bolus of 1 mg/kg and a 4- hour 2.5 mg/kg/h IV infusion.

Distribution
Bivalirudin does not bind to plasma proteins (other than thrombin) or to red blood cells.

Elimination
Bivalirudin has a half-life of 25 minutes in PTCA patients with normal renal function. The total body clearance of bivalirudin in PTCA patients with normal renal function is 3.4 mL/min/kg.

Metabolism
Bivalirudin is metabolized by proteolytic cleavage.

Excretion
Bivalirudin undergoes glomerular filtration. Tubular secretion and tubular reabsorption are also implicated in the excretion of bivalirudin, although the extent is unknown.

Specific Populations
Patients with Renal Impairment: Total body clearance was similar for PTCA patients with normal renal function and with mild renal impairment. Clearance was reduced by 21% in patients with moderate and severe renal impairment with a half- life of 34 and 57 minutes, respectively. In dialysis patients, clearance was reduced by 70%, with a half-life of 3.5 hours.
Approximately 25% bivalirudin is cleared by hemodialysis.