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

Donna S. Cox, Neal Kleiman, Duane A. Boyle, Jagadeesh Aluri, L. Gerald Parchman, Frederick Holdbrook, Michael J. Fossler

Research output: Contribution to journalArticle

25 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)981-990
Number of pages10
JournalJournal of Clinical Pharmacology
Volume44
Issue number9
DOIs
StatePublished - Sep 1 2004

Keywords

  • Activated clotting time
  • Argatroban
  • Percutaneous coronary intervention
  • Pharmacodynamics
  • Pharmacokinetics
  • Platelet GPIIb/IIIa receptor antagonists

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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