Pharmacokinetics and pharmacodynamics of argatroban in combination with a platelet glycoprotein IIB/IIIA receptor antagonist in patients undergoing percutaneous coronary intervention

The pharmocokinetic-pharmocodynamic (PK-PD) relationship of argatrobon, administered in combination with a platelet glycoprotein IIb/IIIa receptor antagonist, was characterized in patients undergoing percutaneous coronary intervention (PCI). Plasma aroatroban and activated clotting times (ACTs) were assessed periprocedurally in 152 patients administered argatroban (250- or 300-mug/kg bolus, then 15-mug/kg/min infusion) in combination with abciximab or eptifibatide during PCI. The PK and PK-PD models were developed utilizing a sequential Population approach in NONMEM. Population PK estimates for clearance, central volume, and peripheral volume were 22.0 L/h, 11.0 L, and 13.0 L, respectively (coefficients of variation [CVs] less than or equal to 10%). By covariate analysis, clearance increased linearly with body weight. Plasma argatroban and ACT effect were well described using a sigmoidal E-max model. For argatroban in combination with platelet glycoprotein IIb/IIIa receptor blockade in patients undergoing PCI, population PK parameters are consistent With values reported for argatroban in healthy subjects. A predictable relationship exists between aroatroban concentration and effect in this setting.