Pharmacokinetic modeling of the high-dose bolus regimen of tirofiban in patients with severe renal impairment.

For the treatment of patients with acute coronary syndromes in the catheterization laboratory, a high-dose bolus (HDB) regimen of tirofiban (25 µg/kg bolus, followed by an infusion of 0.15 µg/kg/min) leads to a consistent and rapid inhibition of platelet aggregation during the first hour after initiation of therapy. The objective of the present study was to use pharmacokinetic modeling to identify an appropriate dosage of tirofiban that would produce a plasma concentration-time profile in patients with severe renal impairment (creatinine clearance<30 ml/min) as similar as possible to that of the HDB regimen in patients with normal renal function. For patients with severe renal impairment, previous recommendations have been to reduce the dosage by 50%. Pharmacokinetic modeling was performed with the following sets of data: the plasma concentrations of tirofiban from patients with normal renal function who were treated with the HDB regimen of tirofiban and the plasma concentrations of tirofiban from patients with severe renal impairment who were treated with a 0.1 µg/kg/min infusion of tirofiban for 1 h. In conclusion, for patients with severe renal impairment, a 25 µg/kg bolus, followed by a 0.10 µg/kg/min maintenance infusion of tirofiban produced a plasma concentration-time profile similar to that observed with the HDB regimen of tirofiban in patients with normal renal function.