TY - JOUR
T1 - Pharmacokinetics and pharmacodynamics of argatroban in combination with a platelet glycoprotein IIB/IIIA receptor antagonist in patients undergoing percutaneous coronary intervention
AU - Cox, Donna S.
AU - Kleiman, Neal S.
AU - Boyle, Duane A.
AU - Aluri, Jagadeesh
AU - Parchman, L. Gerald
AU - Holdbrook, Frederick
AU - Fossler, Michael J.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
KW - Activated clotting time
KW - Argatroban
KW - Percutaneous coronary intervention
KW - Pharmacodynamics
KW - Pharmacokinetics
KW - Platelet GPIIb/IIIa receptor antagonists
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U2 - 10.1177/0091270004267651
DO - 10.1177/0091270004267651
M3 - Article
C2 - 15317826
AN - SCOPUS:4143054608
VL - 44
SP - 981
EP - 990
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
SN - 0091-2700
IS - 9
ER -