Pharmacokinetics and Pharmacodynamics of Argatroban in Combination With a Platelet Glycoprotein IIB/IIIA Receptor Antagonist in Patients Undergoing Percutaneous Coronary Intervention

Publisher Website
Google Scholar
Abstract
The pharmacokinetic‐pharmacodynamic (PK‐PD) relationship of argatroban, administered in combination with a platelet glycoprotein IIb/IIIa receptor antagonist, was characterized in patients undergoing percutaneous coronary intervention (PCI). Plasma argatroban and activated clotting times (ACTs) were assessed periprocedurally in 152 patients administered argatroban (250‐ or 300‐μg/kg bolus, then 15‐μg/ 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] ≤ 10%). By covariate analysis, clearance increased linearly with body weight. Plasma argatroban and ACT effect were well described using a sigmoidal Emax 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 argatroban concentration and effect in this setting.